Bioactive composites of polymer and glass and method for making same

ABSTRACT

The present invention relates to a method of preparing a bioactive composite, the method comprising the steps of a) adding in a solid state a biocompatible polymer and a bioactive glass to an extruder to form an extrudable material; b) applying energy to the extrudable material to at least the melting temperature of the biocompatible polymer to melt mix the biocompatible polymer and bioactive glass; and c) extruding a bioactive composite.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of U.S. patent applicationSer. No. 12/577,835, filed Oct. 13, 2009, which claims the benefit ofthe filing date of U.S. Provisional Patent Application No. 61/141,453,filed Dec. 30, 2008, the disclosures of which are incorporated herein byreference.

BACKGROUND OF THE INVENTION

Biomaterials have been used as implants in the field of spine,orthopaedics and dentistry including trauma, fracture repair,reconstructive surgery and alveolar ridge reconstruction, for over acentury. Although metal implants have been the predominant implants ofchoice for these types of load-bearing applications, additional ceramicsand nonresorbable polymeric materials have been employed within the lasttwenty-five years due to their biocompatibility and physical properties.

Polyetheretherketone (PEEK) is a biomaterial often used in medicalimplants. For example, PEEK can be molded into preselected shapes thatpossess desirable load-bearing properties. PEEK is a thermoplastic withexcellent mechanical properties, including a Young's modulus of about3.6 GPa and a tensile strength of about 100 MPa. PEEK issemi-crystalline, melts at about 340° C., and is resistant to thermaldegradation. Such thermoplastic materials, however, are not bioactive,osteoproductive, or osteoconductive.

Conventional processes do not effectively provide a material or a methodof making the material which combines a biocompatible polymer such asPEEK with a bioactive glass having a particle size larger than onemicron. Furthermore, these processes do not incorporate a material ordisclose a method of making a bioactive implant material which combinesPEEK and bioactive glass of various particle sizes and which has theappropriate structural and mechanical properties to withstand thestresses necessary for use in spinal and orthopaedic implants.

A combination of polymers including PEEK and Combeite glass-ceramic, abioactive glass, has generally been described in U.S. Pat. No.5,681,872; U.S. Pat. No. 5,914,356; and U.S. Pat. No. 6,987,136, each ofwhich is assigned to the assignee of the present invention and isincorporated in this document by reference in its entirety. It has beendiscovered, however, that conventional methods of combiningpolyaryletherketones, such as PEEK, and bioactive glasses, such asCombeite bioactive glass-ceramic, for example, combination using a screwextruder, results in a reaction between the PEEK and the Combeiteglass-ceramic that forms a material having properties which inhibitextruder functioning. In some instances, the reaction makes combiningbioactive materials, such as glass, ceramics, and glass-ceramics, withPEEK, or similar polymers of the polyaryletherketone family, a challengeusing conventional processing. Attempts to combine PEEK and a bioactiveglass without the use of a screw extruder have been made. For example,International Patent Publication WO 2008/039488, which is assigned tothe assignee of the present invention, discloses a method of mixing PEEKand a bioactive glass followed by a compression molding step to form anarticle. Although this process successfully produces a bioactivearticle, the homogeneity of the bioactive article, in part, relies uponthe PEEK and the bioactive glass being processed in powder form so thatthe starting particle size of the PEEK and the particle size of thebioactive glass are closely matched. Furthermore, compression moldingmethods such as this disclosed are not ideal for large scale bulkmaterial preparation.

It is desirable, therefore, to have a process that successfully employsan extruder when producing bioactive composites such as, for example,PEEK and Combeite, because the equipment is readily available and canhandle high throughputs (e.g., on the order of fifty pounds per hour).Furthermore, it is desirable to have a process that yields homogenouspellets which can be re-processed or injected molded to a desired shape(unlike traditional compression molding processes that are subject tovariability in homogeneity, variability in bioactive glass distribution,higher likelihood of structural imperfections, have low yields, and arelimited to small net shapes). Accordingly, there is a need in the artfor a method of preparing a bioactive composite in which a bioactiveglass, such as 45S5 or Combeite, is mixed with a polymer to produce ahomogenous bioactive composite. There is also a need in the art for amethod of preparing a homogeneous bioactive composite which facilitatesuse of various PEEK particle sizes in combination with various bioactiveglass particle sizes (in which the respective particle sizes may bemis-matched). Further, there is also a need in the art for a method forpreparing a bioactive composite in large batches that can be furtherprocessed to produce shaped implants that have the appropriatemechanical properties to withstand the forces required of spinal,orthopaedic and dental implants. The present invention fulfills theseneeds.

BRIEF DESCRIPTION OF SEVERAL VIEWS OF THE DRAWINGS

The invention is best understood from the following detailed descriptionwhen read in connection with the accompanying figures. It is emphasizedthat, according to common practice, the various features of the figuresare not to scale. On the contrary, the dimensions of the variousfeatures are arbitrarily expanded or reduced for clarity. Included arethe following figures:

FIG. 1 provides an isometric view of one embodiment of a cervicalimplant 10.

FIG. 2 provides a front view illustrating the anterior side of thecervical implant 10.

FIG. 3 provides a side view illustrating the medial side of the cervicalimplant 10.

FIGS. 3a and 3b provide side views illustrating the cervical implant 10with and without a lordotic angle, respectively.

FIG. 4 provides a planar view illustrating the substantially trapezoidalshape of the top and bottom surfaces of the cervical implant 10.

FIG. 5 provides an exploded view of the cervical implant 10 with asynthetic graft material.

FIGS. 5a and 5b provide an isometric and top view, respectively, ofanother embodiment of a cervical implant 10 a.

FIG. 6 provides an isometric view of a cervical plate and fastenerassembly 100.

FIG. 7 provides an isometric view of a cervical implant with a cervicalplate and fastener assembly 100.

FIG. 8 provides another view of the cervical implant with the cervicalplate and fastener assembly 100.

FIG. 9 provides an isometric view of an embodiment of a connectoraccessory 110 that may be used in connection with cervical implant 10 or10 a.

FIG. 10 provides an isometric view of another embodiment of a spaceraccessory 120 that may be used in connection with cervical implant 10 or10 a.

FIG. 11 provides an isometric view of the connector accessory 110 andthe spacer accessory 120 that may be used to mate two cervical implants10 or 10 a.

FIG. 12 provides an isometric view of one embodiment of the anteriorlumbar interbody fusion (ALIF) implant 130.

FIG. 13 provides a front view illustrating the anterior side of the ALIFimplant 130.

FIG. 14 provides a side view illustrating the medial side or lateralside of the ALIF implant 130.

FIG. 15 provides an isometric view of an alternate embodiment of theALIF implant 200.

FIG. 16 provides an isometric view of the ALIF implant 200 that includesa fastening feature.

FIG. 17 provides a front view of the ALIF implant and a fasteningfeature.

FIG. 18 provides a side view of the ALIF implant and a fasteningfeature.

FIG. 19 provides a cross-sectional view of the ALIF implant and afastening feature.

FIG. 20 provides an isometric view of one embodiment of the posteriorlumbar interbody fusion (PLIF) implant 240.

FIG. 21 provides an isometric, side view of another embodiment of thePLIF implant 240.

FIG. 22 provides an isometric view of yet another embodiment of the PLIFimplant 240.

FIG. 22a provides an isometric view of one embodiment of atransforaminal lumbar interbody fusion (TLIF) implant x1.

FIG. 22b provides a top and bottom planar view of implant x1.

FIG. 22c provides an isometric view of one embodiment of a TLIF implantillustrating two lateral openings.

FIG. 22d provides a planar view illustrating the openings x12 and x13and recesses on the anterior and posterior sides of the TLIF implant.

FIG. 23 provides an isometric view of one embodiment of the paralleldistraction instrument engaging the ALIF implant 130.

FIG. 24 provides a side view of the parallel distraction instrument 310engaging the ALIF implant 130.

FIG. 25 provides an exploded view of the pair of upper 320 and lowerforks 330 of the parallel distraction instrument 310.

FIG. 26 provides a detailed, isometric view of the parallel distractioninstrument 310.

FIG. 27 provides an isometric view of the parallel distractioninstrument 310 illustrating the grasping end 340 or handle of theinstrument.

FIG. 28 provides an isometric view of one embodiment of the implantinsertion tool 350.

FIG. 29 provides a detailed view of the tip of the implant insertiontool 350.

FIG. 30 provides an isometric view of another embodiment of the implantinsertion tool 350 featuring a threaded tip.

FIG. 31 provides a detailed, isometric view of the implant insertiontool 350 about to engage the ALIF implant 130.

FIG. 31a provides an isometric view of another embodiment of the implantinsertion tool 350 featuring a threaded tip that can be advanced viarotation of the advancer 380 or rotatable end knob 380 a.

FIG. 32 provides an isometric view of implant insertion tool 390 priorto engaging cervical implant 10.

FIG. 33 provides an isometric view of implant insertion tool 390engaging cervical implant 10.

FIG. 34 provides a side view of implant insertion tool 390 insertingcervical implant 10 between two vertebral bodies.

FIG. 35 provides a side view of another embodiment of the implantinsertion tool 410 inserting the cervical implant 10 between twovertebral bodies.

FIG. 36 provides a planar view of one embodiment of forceps 440.

FIG. 37 provides a detailed, planar view of the forceps 440 engagingcervical implant 10.

FIG. 38 provides an isometric view of the forceps 440 engaging thecervical implant 10.

FIG. 39 provides a detailed, isometric view of the forceps 440 engagingthe cervical implant 10.

FIG. 40 provides an exploded, isometric view of one embodiment of theinsertion tool 470 of the present invention.

FIG. 41 provides an isometric view of the assembled insertion tool 470.

FIG. 42 provides an isometric view of another embodiment of theinsertion tool 500.

FIG. 43 provides a detailed isometric view of an embodiment of theinsertion tool 500 of the present invention engaging the cervicalimplant 10.

FIG. 44 provides an isometric view of the insertion tool 500 and oneembodiment of the impactor hammer 510 of the present invention.

FIG. 45 provides an isometric view of the insertion tool 500 and thecervical implant 10 being inserted between two vertebral bodies.

FIG. 46 provides a side view of the insertion tool 500 and the cervicalimplant 10 being inserted between two vertebral bodies.

FIGS. 47a through 47c provide a front view of the insertion tool 500being used to adjust the position of the implant 10 between the twovertebral bodies.

FIG. 47d provides a side view illustrating a rasp instrument y1 of thepresent invention to be used to shape the endplate prior to implantinsertion.

FIG. 48 provides isometric views of one embodiment of trial implanttools of the present invention.

FIG. 49 provides a detailed, isometric view of the trial implant of FIG.48.

FIG. 50 provides an isometric view of one embodiment of the graftimpaction block 540 of the present invention.

FIG. 51 provides an isometric view of the graft impaction block 540 andthe forceps tool 440 engaging the cervical implant 10.

FIG. 52 provides an isometric view of the graft impaction block 540 andthe insertion of graft material into the cervical implant 10.

FIG. 53 is an example of another embodiment of a shaped body in the formof a vertebral body spinal implant according to the present invention.

FIG. 54 is an example of another embodiment of a shaped body in the formof a vertebral body spinal implant according to the present inventionshown with a graft material in the center of the implant.

FIG. 55, FIG. 56, FIG. 57 show various bone dowels for spinal fusion inplace in the vertebral body (vertebral body shown in phantom).

FIG. 58 is an example of one embodiment of a shaped body in the form ofan orthopaedic hip implant according to the present invention.

FIGS. 59a and 59b depict insertion of femoral hip dowels into a femur(femur shown in phantom in each figure).

FIGS. 60a through d depict different forms of dowels for orthopaedicuse.

FIGS. 61a and 61b illustrate an embodiment of the material of thepresent invention shaped into a sleeve form and used for impactiongrafting to accommodate an artificial implant said sleeve form beingscrewed, bonded, pinned or otherwise attached in place.

FIG. 62 illustrates an embodiment of the material of the presentinvention shaped into a block or sleeve form and used for the repair orreplacement of bulk defects in bone, oncology defects or screwaugmentation.

FIG. 63 is an example of one embodiment of a shaped body in the form ofscrews according to the present invention.

FIG. 64 is an example of one embodiment of a shaped body in the form oforthopaedic plates according to the present invention.

FIGS. 65a, 65b and 65c depict synthetic cortical vertebral spacers orinterbody devices comprised of the material of the present invention.FIGS. 65b and 65c are in the shape of rings.

FIGS. 66a through c depict synthetic cortical bone dowels or interbodydevices comprised of the material of the present invention.

FIG. 67 is another form of synthetic cortical spacer comprised of thematerial of the present invention.

FIG. 68 is a synthetic cortical vertebral interbody device comprised ofthe material of the present invention.

FIG. 69 is a synthetic shaped body for bone restoration. The bioactivecomposite of the present invention 270 a is combined with a calciumphosphate portion 272 a to give rise to a bioactive cortico-cancellousshaped body.

FIG. 70 is a synthetic cortical ring comprised of the material of thepresent invention.

FIG. 71 is a synthetic cortical rod for orthopaedic restorationcomprised of the material of the present invention.

FIGS. 72a and 72b illustrate another embodiment of the present inventionused as a cranio-maxillofacial, zygomatic reconstruction and mandibularimplant.

FIGS. 73a and 73b illustrate one embodiment of the material of thepresent invention shaped into a block form and used as a tibial plateaureconstruction that is screwed, bonded, cemented, pinned, anchored, orotherwise attached in place.

FIG. 74 is an example of one embodiment of a shaped body in the form ofa dental implant according to the present invention.

FIG. 75a and FIG. 75b illustrate one embodiment of the present inventionused as a sleeve in which a tooth is screwed, bonded, cemented, pinned,anchored, or otherwise attached in place.

FIG. 76 depicts a series of scanning electron microscope (SEM)photographs of various sample embodiments of the present inventioncomprising PEEK and Combeite glass-ceramic (<53 μm) prior to immersionin simulated body fluid (SBF).

FIG. 77 depicts a series of SEM photographs of the samples shown in FIG.76 after immersion in SBF for 3 days.

FIG. 78 depicts a series of SEM photographs of the samples shown in FIG.76 after immersion in SBF for 7 days.

FIG. 79 depicts a series of SEM photographs of certain of the samplesshown in FIG. 76 after immersion in SBF for 14 days.

FIG. 80 depicts a series of SEM photographs of certain of the samplesshown in FIG. 76 after immersion in SBF for 21 days.

FIG. 81 depicts a SEM photograph showing a cross sectional view of anexemplary embodiment of the present invention comprising 60% PEEK and40% Combeite glass-ceramic (<53 μm) after immersion in SBF for 21 daysalong with an energy dispersive spectroscopy (EDS) spectrum of thelayers confirming calcium phosphate (CaP) growth.

FIG. 82 depicts a series of SEM photographs of certain of the samplesshown in FIG. 76 after immersion in SBF for 28 days.

FIG. 83 depicts a series of SEM photographs of various sampleembodiments of the present invention comprising PEEK and Combeiteglass-ceramic (90 to 150 μm) prior to and after immersion in SBF for upto 14 days.

FIG. 84 depicts SEM photographs of an exemplary embodiment of thecomposite shaped body of the present invention comprising 80% PEEK and20% Combeite glass-ceramic (90 to 150 μm) before and after immersion inSBF for 7 days.

FIG. 85 depicts SEM photographs of an exemplary embodiment of thecomposite shaped body of the present invention comprising 70% PEEK and30% Combeite glass-ceramic (90 to 150 μm) before and after immersion inSBF for 7 days.

FIG. 86 depicts microCT images and 3-D reconstructions of an exemplaryembodiment of the present invention comprising 80% PEEK and 20% Combeiteglass-ceramic (90 to 150 μm).

FIG. 87 depicts microCT images and 3-D reconstructions of an exemplaryembodiment of the present invention comprising 70% PEEK and 30% Combeiteglass-ceramic (90 to 150 μm).

FIG. 88 depicts the maximum interfacial shear strength at thematerial-bone interface of various embodiments of the present inventionafter 12 and 24 weeks of implantation in a sheep long bone.

FIG. 89 is a histological image after in-vivo implantation of a dowelcomprised of the material of the present invention showing bone adjacentto and growing into the implant without intervening fibrous tissue.

FIG. 90 is a histological image after in-vivo implantation of anotherdowel comprised of the material of the present invention showing boneadjacent to and growing into the implant without intervening fibroustissue.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates generally to bioactive composites ofbiocompatible polymer and glass and, more particularly, to implants. Thepresent invention also relates to methods of manufacturing bioactivecomposites. The present invention further relates to methods ofrepairing or fusing bone; methods of replacing diseased or dysfunctionaljoints; methods of implanting bioactive composites of polymer and glass;and methods of facilitating mechanical interlock of composite implantswith bone.

The present invention provides bioactive composites, and methods formaking the bioactive composites, comprising bioactive and biocompatibleimplant materials for formulation of shaped bodies capable of bondingand mechanically interlocking to bone. The present invention alsoprovides bioactive composites and methods to produce shaped implantsthat have the appropriate mechanical properties to withstand the forcesrequired of spinal, orthopaedic and dental implants. The presentinvention further provides methods for preparing bioactive compositescomprising a biocompatible polymer such as, for example,polyetheretherketone (PEEK), and a bioactive glass such as, for example,Combeite glass-ceramic. The present invention also provides for shapedbodies prepared from these materials to be used in a wide array ofclinical applications.

In one embodiment, the present invention provides bioactive compositesthat include a biocompatible polymer in combination with a bioactiveglass. As used herein, the term “biocompatible polymer” refers to apolymer that, when introduced into a living system, will be compatiblewith living tissue or the living system (e.g., by not beingsubstantially toxic, injurious, or not causing immunological rejection).The biocompatible polymer may be selected such that it will function toreinforce the composite in order to, for example, increase the loadbearing capability of the composite.

The biocompatible polymer used in the present invention is preferably asynthetic polymer. Examples of synthetic biocompatible polymers that aresuitable for use in the present invention alone or in combinationinclude, polymethylmethacrylate, polyaryletherketones (PAEKs), includingpolyetheretherketone (PEEK) and polyaryletherketone-etherketoneketone(PEKEKK), polyurethane, poly(L-lactide), poly(D,L-lactide),poly(L-co-D,L-lactide), polyglycolide, poly(lactide-co-glycolide),poly(hydroxylbutyrate), poly(hydroxyvalerate), tyrosine-derivedpolycarbonate, polyanhydride, polyorthoester, polyphosphazene,poly(dioxanone), poly(ε-caprolactone), and polyglyconate. Other similarpolymers known in the art may be used and various combinations ofpolymers may be included in the composition to adjust the properties ofthe composition as desired. In preferred embodiments of the presentinvention, polymers in the PAEK family, including PEEK are the preferredbiocompatible polymers.

The molecular weight of the biocompatible polymer may vary depending onthe desired application. Preferred molecular weights of the polymersinclude from about 50,000 to about 750,000, from about 50,000 to about500,000 and from about 70,000 to about 400,000 Daltons. In someembodiments where PEEK is used as the biocompatible polymer, the PEEKmay be high molecular weight PEEK (i.e., 110,000-120,000 M_(n)), mediummolecular weight PEEK (i.e., 100,000-110,000 M_(n)) or low molecularweight PEEK (i.e., 70,000-100,000 M_(n)). For instance, high molecularweight PEEK may be preferred for processes in which the glass load islow; whereas low molecular weight PEEK may be more preferred forprocesses in which the glass load is high. Low molecular weight PEEK mayalso be preferred for applications where the final molded implantpossesses intricate design features or requires repeated re-meltingsteps. Alternatively, the biocompatible polymer itself may be a mediummolecular weight PEEK or a composite of high and low molecular weightPEEK. The preferred biocompatible polymer may have a melt flow rate(ASTM D1238) from 1 g/10 min to 60 g/10 min. In certain embodiments, thepolymer has a high molecular weight and the melt flow rate is from 2 to5 g/10 min. In other embodiments, the polymer has a low molecular weightand the melt flow rate is 18-50 g/10 min. Non-limiting representativeexamples of PEEK polymers include Invibio®'s PEEK-OPTIMA® LT1 (highmolecular weight), PEEK-OPTIMA® LT2 (medium molecular weight),PEEK-OPTIMA® LT3 (low molecular weight), MOTIS™, PEEK-CLASSIX® (Invibio,Ltd., Lancashire, United Kingdom; Invibio, Inc., West Conshohocken,Pa.), PEEK polymers from Evonik Degussa Corporation (Parsippany, N.J.),PEEK Altera™ from Medshape Solutions, Inc (Atlanta, Ga.), and Zeniva™from Solvay Advanced Polymers, LLC (Alpharetta, Ga.).

The biocompatible polymer component of the present invention can be usedin a wide range of particle sizes. For instance, the biocompatiblepolymer may have a particle size of from about 4 μm to about 4,000 μm.In a preferred embodiment of the present invention, the particle sizeranges from about 1000 μm to about 4,000 μm. In such embodiments, thebiocompatible polymer is typically obtained in granular or pellet formfrom a commercial supplier before it is mixed with the bioactive glassin accordance with the methods of the present invention.

Bioactive glasses and glass-ceramics are characterized by their abilityto form a direct bond with bone. A material based on the PEEK polymer,or similar types of polymers of the PEEK family that include thebone-bonding properties of a bioactive glass, would be desirable. Byincorporating bioactive glass into the polymer matrix, a compositematerial is formed which when implanted elicits a bioactive reaction andleads to bone formation and direct bone apposition onto the surface ofthe implant, usually without intervening fibrous tissue. It has beenparticularly determined that bioactive glass in the size range of fromabout 50 μm to about 300 μm, and, more particularly, from about 90 μm toabout 150 μm facilitates mechanical interlock of the composite materialwith bone, such that bone grows into the surface of the bioactivecomposite at the site of the bioactive particle.

The bioactive glass used in the present invention may be anyalkali-containing ceramic (glass, glass-ceramic, or crystalline)material that reacts as it comes in contact with physiological fluidsincluding, but not limited to, blood and serum, which leads to boneformation. In preferred embodiments, the bioactive glasses, when placedin physiologic fluids, form an apatite layer on their surface. As usedherein, “bioactive” relates to the chemical formation of a calciumphosphate layer (amorphous, partially crystalline, or crystalline) viaion exchange between surrounding fluid and the composite material.Bioactive also describes materials that, when subjected tointracorporeal implantation, elicit a reaction. Such a reaction leads tobone formation, attachment into or adjacent to the implant, and/or boneformation or apposition directly to the implant, usually withoutintervening fibrous tissue.

Preferably, the bioactive glass component of the present inventioncomprises regions of Combeite crystallite morphology. Such bioactiveglass is referred to in this document as “Combeite glass-ceramic”.Examples of preferred bioactive glasses suitable for use in the presentinvention are described in U.S. Pat. No. 5,914,356 and U.S. Pat. No.5,681,872, each of which is incorporated by reference in this documentin its entirety. Other suitable bioactive materials include 45S5 glassand compositions comprising calcium-phosphorous-sodium silicate andcalcium-phosphorous silicate. Further bioactive glass compositions thatmay be suitable for use in the present invention are described in U.S.Pat. No. 6,709,744, incorporated in this document by reference. Othersuitable bioactive glasses include borosilicate, silica, andWollastonite. Suitable bioactive glasses include, but are not limitedto, silica-, borate-, and phosphate-containing materials. It isunderstood that some non-alkali-containing bioactive glass materials arewithin the spirit of the invention. Bioactive glasses, as defined inthis document, do not include calcium phosphate materials, for example,hydroxyapatite and tri-calcium phosphate. However, in addition tobioactive glass, the composition of the invention may additionallyinclude other agents such as calcium phosphate materials.

In preferred embodiments of the present invention, the bioactive glassis Combeite glass-ceramic (also referred to as “Combeite”). Combeite isa mineral having the chemical composition Na₄Ca₃Si₆O₁₆(OH)₂. It has beenfound that the use of bioactive glass in restorative compositions, whichbioactive glasses include Combeite crystallites in a glass-ceramicstructure (hence, Combeite glass-ceramic), in accordance with thepresent invention gives rise to superior spinal, orthopaedic and dentalrestorations.

It is preferred that the Combeite glass-ceramic particles which formsome or all of the bioactive glass component of the present inventioncomprise at least about 2% by volume of Combeite crystallites. Combeiteglass-ceramic particles containing higher percentages of crystallitesare more preferred and volume percentage from about 5% to about 50% ofcrystallites are particularly desired. It will be appreciated that theCombeite glass-ceramic particles of the present invention areheterogeneous in that they comprise a glassy, amorphous structure havingcrystallites or regions of Combeite crystallinity dispersed throughoutthe material.

It is preferred that the heterogeneous particles of Combeiteglass-ceramic have an average particle size from about 1 μm to about 500μm. In some embodiments of the present invention, the Combeiteglass-ceramic has an average particle size of less than about 300 μm. Inother embodiments of the present invention, the Combeite glass-ceramichas an average particle size of less than about 150 μm. In still otherembodiments of the present invention, the Combeite glass-ceramic has anaverage particle size of less than about 53 μm.

Several particular Combeite glass-ceramic average particle size rangeshave been found to be preferred when practiced with the presentinvention. The first range is less than or equal to about 53 μm. Thenext average particle size range is less than or equal to about 90 μm.The third average particle size range is from about 90 μm to about 150μm. The fourth average particle size range is less than or equal toabout 150 μm. It is envisioned that, in certain embodiments of thepresent invention, the bioactive particles are nanoparticulate. It isalso contemplated that a mix of bioactive particles of differing averageparticle sizes may be used.

Methods of determining particle sizes are known in the art. Some methodsinclude passing the particles through several sieves to determinegeneral particle size ranges. Other methods include laser lightscattering, and still others are known to persons skilled in the art.Determination of particle size is conveniently accomplished by sievingand such may be used here. Particle size may also be determined via SEMimage analysis. It will be appreciated that recitation of averages orsize ranges is not meant to exclude every particle with a slightlyhigher or lower dimension. Rather, sizes of particles are definedpractically and in the context of this invention.

In accordance with some preferred embodiments, blends of Combeiteglass-ceramics may be useful as the bioactive glass component of thepresent invention. Thus, a number of different Combeite glass-ceramicscan be prepared having different properties, such as Combeitecrystallite size, percentage of Combeite crystallites, particle sizes ofthe Combeite glass-ceramic and the like. It is also preferred in somecases to admix Combeite glass-ceramic in accordance with the presentinvention with other agents which are consistent with the objectives tobe obtained. Thus, a wide variety of such other agents may be soemployed so long as composition of the invention comprises bioactiveglass equaling at least about 5% by weight of the composition. The otheragent composition may also include radiopacifying agents such as thoseknown in the art.

In certain embodiments, the bioactive glass component may be in the formof fibers, whiskers or strands. It is preferred that the diameters ofthese fibers and strands be from about 1 μm to about 500 μm.

In some embodiments, the bioactive glass comprises at least one alkalimetal such as, for example, lithium, sodium, potassium, rubidium,cesium, francium, or combinations of these metals. In other embodiments,however, the bioactive glass has little to no alkali metal. For example,in certain embodiments, the bioactive glass has 30% or less of alkalimetal. In other embodiments, the bioactive glass has 25% or less ofalkali metal. In yet other embodiments, the bioactive glass has 20% orless of alkali metal. In yet other embodiments, the bioactive glass has15% or less of alkali metal. In other embodiments, the bioactive glasshas 10% or less of alkali metal. In still other embodiments, thebioactive glass has 5% or less of alkali metal. In yet otherembodiments, the bioactive glass has substantially no alkali metal.Without intending to be bound by any particular theory, it is believedthat the presence of certain metals may catalyze further polymerizationof the biocompatible polymer such as, for example, PEEK, thereby (1)increasing its molecular weight and/or (2) increasing its degree ofcross-linking/cross-link density. Either event increases the viscosityof the polymer and may seize up the equipment used to process thecomposite material. As such, a bioactive glass with a low percentage ofalkali metal may be utilized to prevent equipment failure and/or toallow a high percentage of bioactive glass to be utilized.

In exemplary embodiments of the present invention, the bioactive glasshas osteoproductive properties. As used in this document,“osteoproductive” refers to an ability to allow osteoblasts toproliferate, allowing bone to regenerate. “Osteoproductive” may also bedefined as conducive to a process in which a bioactive surface iscolonized by osteogenic stem cells and which results in more rapidfilling of defects than that produced by merely osteoconductivematerials. Combeite glass-ceramic is an example of an osteoproductive,bioactive material.

According to one embodiment of the present invention, the compoundedcomposite material may comprise up to about 50% of the bioactive glass.In certain embodiments, the bioactive glass is present in an amount ofabout 5 to 50% by weight of the compounded composite material. In otherembodiments, the bioactive glass is present in an amount of about 15 to30% by weight of the compounded composite material. In yet otherembodiments, the bioactive glass is present in an amount of about 20 to30% by weight of the compounded composite material. In embodiments inwhich a low molecular weight biocompatible polymer is used, bioactiveglass may be present in higher weight percentages, such as 60% by weightof the compounded composite material.

In some embodiments of the present invention, a coupling agent is addedto the mixture of the biocompatible polymer and the bioactive glass. Thecoupling agent acts as a bonding agent between the biocompatible polymerand the bioactive glass which translates into increased tensile/flexuralstrength of the bioactive composite. Non-limiting examples of couplingagents suitable for use in the present invention include, for example,silane, titanium-based and zirconium-based coupling agents,specifically, organotitanate, multifunctional amine compounds such as4-aminophenyl sulfone, azo compounds such as 4-cyanovaleric acid, andcombinations thereof. The preferred coupling agent is one that includesmultifunctional groups that are capable of chemically bonding with afunctional group of the biocompatible polymer and binding the bioactiveglass. The bioactive glass may be coated with the coupling agent priorto being combined/mixed with the biocompatible polymer. Alternatively,both the bioactive glass and biocompatible polymer may be individuallycoated with the coupling agent before being combined.

Also in accordance with the present invention, at least one other agentmay be added to the mixture of the biocompatible polymer and bioactiveglass. Such agents can comprise, at least partially, reinforcing fibers.Non-limiting examples of other agents include carbon, glass, radiopaquematerial, barium glass, resorbable material, strontium, strontiumnitrate, strontium-calcium-zinc-silicate glasses, silver, calciumapatite, calcium silicate or mixtures of these materials. In certainaspects of the invention, the other agent is barium sulfate,barium-boroaluminosilicate (BBAS) glass, silica or e-glass fibers. Insome embodiments, the other agents include radiopaque markers situatedin predetermined locations within the shaped implant to aid invisualizing the implant once in the body. For example, FIGS. 5a and 5bshow titanium alloy (Ti-6Al-4V ELI) markers incorporated into thecomposite shaped body. In certain embodiments, the other agent maycomprise calcium phosphate having macro-, meso-, and microporosity. Morepreferably, the porosity of the calcium phosphate is interconnected. Thepreparation of preferred forms of calcium phosphate for use in thepresent invention is described in U.S. Pat. No. 6,383,519 and U.S. Pat.No. 6,521,246, incorporated into this application by reference in theirentireties. An exemplary calcium phosphate product is Vitoss® Bone GraftSubstitute (available from Orthovita, Inc. of Malvern, Pa.). The atleast one other agent may be incorporated within the bioactivecomposite, or in the case of a shaped implant be used to fill cavitiesof the implant. For instance, when used with a shaped spinal implant,the other agent may be present within the center cavity of the implantto facilitate fusion of the adjacent vertebral bodies (FIG. 54).

In addition to other agents, bone augmentation materials or bone cementsmay be used in conjunction with the bioactive composite in applicationswhere additional reinforcement is required. For instance, in certainbone fractures it may first be required that certain portions of thefracture be stabilized with a bone augmentation material prior toplacing the bioactive composite implant of the present invention.Alternatively, in certain spine fusion procedures, it may first bedesired to prophylactically treat the adjacent vertebrae prior toplacing the bioactive spinal implant of the present invention in thedisc space between the two vertebrae, if the bone stock appears weakeneddue to trauma or disease such as osteoporosis. An exemplary boneaugmentation product is Cortoss® Bone Augmentation Material (availablefrom Orthovita, Inc. of Malvern, Pa.).

In a preferred embodiment of the present invention, a bioactivecomposite is formed upon combining a biocompatible polymer with abioactive glass as described in the present invention. The biocompatiblepolymer preferably has a particle size range from 400 μm to 4,000 μm andcomprises from about 60-90% by weight of the composite composition andthe bioactive glass has a particle size range of from about 1 μm toabout 500 μm and comprises from about 10-40% by weight of the compositecomposition. The use of low molecular weight PEEK has been determined tofacilitate processing of the composite.

It has been found that the use of low molecular weight PEEK andparticularly low molecular weight PEEK having a large particle size(e.g., particles from 400 μm to 4,000 μm) as used in the preferredembodiment of the present invention unexpectedly allows processing usingextrusion, enables homogeneity of the composite to be achieved even whenthe size of the PEEK particles is not evenly matched to the size of thebioactive glass particles, and improves structural fidelity.Furthermore, the use of low molecular weight PEEK particles inconjunction with bioactive glass as described herein, results in a novelbioactive, bone-bonding composition having suitable physical propertiesfor use in a variety of spinal, orthopaedics and dental surgicalprocedures.

The present invention also provides a method of preparing a bioactivecomposite, the method comprising the steps of: a) adding to a compoundera biocompatible polymer and a bioactive glass to form an extrudablecomposite material, wherein i. the bioactive glass has a particle sizeof from about 1 μm to about 500 μm; ii. the bioactive glass is presentin the extrudable composite material in an amount of from about 5 toabout 50% by weight; and b) applying energy (e.g., heat, vibrational,radiofrequency, microwave, etc., or combinations thereof) to theextrudable composite material to mix the biocompatible polymer and thebioactive glass; and c) extruding a bioactive composite. The presentinvention also provides a method of preparing a bioactive composite, themethod comprising the steps of: a) adding to a compounder abiocompatible polymer; b) applying energy (e.g., heat, vibrational,radiofrequency, microwave, etc., or combinations thereof) to thebiocompatible polymer for a period of time and temperature to form amelted polymer; c) adding to the melted polymer a bioactive glass toform a composite material, wherein i. the bioactive glass has a particlesize range of from about 1 μm to about 500 μm; ii. the bioactive glassis present in the extrudable composite material in an amount of fromabout 5 to about 50% by weight; and d) allowing the composite materialto travel down the length of the heated barrel for additional time tomelt mix the biocompatible polymer and the bioactive glass; and e)extruding a homogenous bioactive composite. The bioactive composite canbe extruded in the form of films, sheets, rods, and the like, thoughpreferably the bioactive composite is extruded and pelletized, such thatthe pellets can then be re-processed to form the desired shape. In oneembodiment, the bioactive composite is extruded into pellets (e.g.,homogeneous bioactive composite pellets) in the size range from about400 μm to about 4000 μm. In another embodiment, the bioactive compositemay be extruded into pellets in the size range of about 1000 μm to about4000 μm.

It should be noted that the step of adding the bioactive glass to thepolymer can be performed at various stages of the compounding process.For instance, the bioactive glass can be blended with the polymer priorto adding the mixture to the compounder. The bioactive glass can also beadded using a second downstream hopper once the polymer has traveled anadequate distance along the length of the barrel such that it issufficiently softened or such that it is in a completely melted state.Most preferably, the bioactive glass is added to the melted polymer at apoint downstream such that the polymer-glass mixture only travels thedistance of the barrel that is necessary to produce a homogenous mixtureprior to extruding. It will be appreciated that there are numerous typesof compounders known in the art with varying barrel diameters, barrellengths, and screw types. Preferably, the method of the presentinvention utilizes a twin screw extruder and the bioactive glass isadded to the polymer once the polymer is in a completely melted state,typically after it has traveled at least 50% of the length of thebarrel. However it should be appreciated that the method of the presentinvention can be utilized with any combination of barrel diameter,barrel length, or screw type by modifying the distance downstream thatthe bioactive glass is added to the polymer.

In other embodiments, the biocompatible polymer and the bioactive glass(as well as other components, if present) may be dry mixed for a periodof time and under conditions sufficient to achieve substantialhomogeneity of the mixture. As used herein, the term “dry mixed” refersto mixing the components in a dry state, i.e., in the absence of addedliquid water or organic solvent. The dry mixing of the bioactive glasswith the biocompatible polymer granules or pellets may be accomplishedusing any methods known in the art per se, including milling, spinning,tumbling, sonication, vibrating, or shaking. In one embodiment, themixture is tumbled on rollers for about one to about two hours. As usedherein, the terms “homogeneity” and “homogeneous” describe a compositionthat is substantially uniform in structure and/or compositionthroughout. The term “substantially homogeneous” is to be understoodwithin the context of the invention and is not to be taken as anabsolute.

In one embodiment, the extrudable composite material is formed by addingthe polymer and bioactive glass to a compounder such as, for example, asingle screw or a twin screw extruder, where it is melt mixed andextruded to form a bioactive composite. It is a feature of the presentinvention that the biocompatible polymer is melt mixed with thebioactive glass. As used herein, the term “melt mixed” or “compounded”refers to mixing the components using heat and shear. For example, thebiocompatible polymer may be compounded by placing in a screw extruder,melting via heat and then adding the bioactive glass to the extruderafter the biocompatible polymer is melted. The biocompatible polymer mayalso be dry mixed with the bioactive glass as detailed above to form anextrudable composite material. In a preferred embodiment, thebiocompatible polymer and bioactive glass are mixed without the use ofliquids/fluids such as water or organic solvents including ethanol. Inother embodiments, the use of a solvent is prohibited in the sense thatthe solvent can cause irreparable damage to the extruder. In thismanner, the present invention differs from that of International PatentPublication WO 2008/039488, assigned to the assignee of the presentinvention, because International Patent Publication WO 2008/039488focuses on the use of a solvent to mix biocompatible polymer andbioactive glass of similar particle size. By eliminating the use of asolvent, the bioactive glass retains its inherent bioactivity and is notpre-leached. Various methods of compounding the material can be utilizedto increase the percentage of bioactive glass and/or allow forsubsequent re-heating of the composite material. For example, using asingle screw extruder reduces the shear forces. Reducing the contacttime between the bioactive glass and polymer in the compounder will alsoallow for a greater percentage of bioactive glass to be incorporated,for example, by adding the bioactive glass at a point downstream in thebarrel once the polymer is already melted. It is preferable to use atwin screw compounder to produce the bioactive composite of the presentinvention, due to increased homogeneity of the resultant composite. Mostpreferably, the bioactive glass is added to the twin screw extruderusing a second hopper at a point downstream in the barrel where thepolymer is already in a melted state. The second hopper is positionedalong the length of the barrel such that the bioactive glass travels theshortest distance possible in contact with the melted polymer to producea homogenously mixed composite, generally less than 50% of the length ofthe barrel. One non-limiting example of a compounder that may be used tocompound the biocompatible polymer and bioactive glass components of thepresent invention is the Leistritz 40 mm twin screw extruder (Model ZSE40HP).

In the extruder the composition is first melt mixed using, for example,twin high shear screws and formed into a continuous strand of bioactivecomposite which is further pelletized into molding granules (pellets).The melt mix typically promotes uniformity in the dispersion of the PEEKand the bioactive glass and facilitates the use of a various sizes ofparticles (e.g., PEEK particles may differ in size from the size of thebioactive glass particles) while still producing a homogeneouscomposite. The temperature needed to melt mix the biocompatible polymerand the bioactive glass will typically depend on the melting temperatureof the biocompatible polymer being used. For example, when thebiocompatible polymer is PEEK, generally the melt mixing temperaturewill be at least 340° C., typically from about 340 to about 400° C.Under this condition, the PEEK is sufficiently fluidized in thecomposition and uniformly coats the bioactive glass component.

The amount of torque required to extrude the melt mix from thecompounder will depend on a number of factors such as, for example, theinherent viscosity of the biocompatible polymer, the RPMs (revolutionsper minute), the inherent capability of the extruder, and the kind andamount of the bioactive glass. For example, Table 1 demonstrates theeffect of such factors on torque for a Theysohn TSK 21 mm Twin ScrewExtruder (Theysohn Extruders, Korneuburg, Austria) at a barreltemperature of 380° C. It can be appreciated that the torque and RPMsrequired for low molecular weight PEEK are relatively unaffected by thepercentage of glass filler. The torque and RPMs required to extrudecomposites of high molecular weight increase with increasing amounts ofbioactive glass. This effect is more pronounced with smaller sizedbioactive glass particles.

TABLE 1 % PEEK/ Torque Grade of PEEK % Combeite (Nm) RPMs Low Molecular100/0  36 256 Weight* w/<53 μm 85/15 37.44 260 glass 70/30 38.90 268High Molecular 100/0  50.4 250 Weight* w/<53 μm 85/15 52.6 300 glass80/20 54.72 350 70/30 51.8 400 High Molecular 100/0  50.4 250 WeightMedical 85/15 55.44 300 Grade** 80/20 57.6 350 w/<53 μm glass 70/3054.72 400 High Molecular 100/0  50.4 250 Weight* w/90-150 μm 85/15 53.3284 glass 80/20 50.4 317 70/30 49.0 340 High Molecular 100/0  50.4 250Weight* w/silane- 85/15 48.24 285 treated <53 μm 80/20 46.8 317 glass70/30 51.84 339 *= obtained from Victrex, West Conshohocken, PA **=obtained from Invibio Biomaterial Solutions, West Conshohocken, PA

The pellets/granules of bioactive composite are ready for injectionmolding either immediately after the extrusion process or after a periodof storage. The resultant extrudate is a bioactive composite that can bethe final molded article, such as in the case of an injection moldedarticle or an extruded tube, sheet or coating, or can be chopped intomolding pellets/granules for subsequent melt processing into the articledesired. One non-limiting example of a molder that may be employed tomold the composite pellets of the present invention is the CincinnatiRoboshot S2000i B 55 ton molder.

The bioactive composite can be molded using conventional moldingtechniques, including compression and injection molding. In addition,conventional machining techniques can be used to form an integral shapedbioactive implant body, such as those exemplary embodiments depicted inthe figures. The bioactive composite may be injection molded into ashaped implant body. Preferably, the bioactive composite may be moldedin a near net shape such that after further machining, a shaped body forimplantation is prepared. For example, the bioactive composite may bemolded to form a generic shape, for example a cylinder, block, or ovoid,which is then machined to a pre-selected implant shape.

In a typical injection molding process of thermoplastics, the bioactivecomposite pellets are heated to a temperature at which the compositebecomes molten and the molten composite is injected into a mold followedby cooling to room temperature or below. Alternatively, the bioactivecomposite pellets can be compression molded to form the implant body. Inthis embodiment, a mold is filled with the composite pellets and apressure of, for example, about 1 to about 400 MPa is applied to form abioactive implant or a generic shape suitable for further machining.Heat sufficient to melt at least one component of the composite can alsobe used. In addition to using heat to melt at least one component of thecomposite, vibrational, radiofrequency, or microwave energy, orcombinations of these energies, can be used to melt at least onecomponent of the composite.

In another embodiment of the present invention, the bioactive polymerand the bioactive glass can be added directly to an injection molderwithout first performing a compounding step. In such embodiment, themethod of the invention comprises the steps of: adding in a solid statethe biocompatible polymer and the bioactive glass to an injection molderto form a shaped bioactive composite, wherein the bioactive glass has aparticle size of from about 1 μm to about 500 μm; and the bioactiveglass is present in the composite in an amount of from about 5 to about50% by weight; applying energy to the injection molder to form a meltmix of the biocompatible polymer and the bioactive glass; and injectingthe melt mix into a mold to form the shaped bioactive composite. Thebiocompatible polymer and the bioactive glass can be added to theinjection molder pre-mixed or they can be added separately. By eithermethod of addition, the biocompatible polymer and the bioactive glassare melt mixed in the injection molder.

Once the bioactive composite has been molded into its final form, themolded bioactive composite is preferably subjected to a finishing stepto further expose the bioactive glass. Examples of finishing techniquesinclude, for example, milling, cutting, drilling, and/or sanding of theshaped body. Additionally, exposure of the bioactive glass could beaccomplished through grit blasting, plasma treatments, etching and thelike. Preferred embodiments of the present invention have from about 3%to about 30% surface area exposure of bioactive glass. This amount ofsurface exposure allows for the bioactive reaction initiating at theglass particle to uniformly spread across the composite surface. Thisamount of exposed bioactive glass further lends a surface roughness tothe implant which is favorable for bone bonding, and the remodeling ofglass particles at the surface leads to a mechanical interlock betweenthe implant and the newly formed bone.

Bioactive composite implant structures contemplated by the presentinvention include homogeneous composites prepared by mixing abiocompatible polymer such as, for example, PEEK, with bioactive glass,using the methods described. In certain embodiments, the mean particleto particle distance (e.g., mean separation of bioactive glass particlesas measured from the edges of the particles) throughout the volume andalong the surface is about 80 microns to about 180 microns. For example,the mean particle to particle distance in an embodiment, in which thebioactive composite is 80% by weight high molecular weight polymer and20% by weight bioactive glass (having a particle size of 90 μm to 150μm), may be between about 140 μm to about 180 μm. In another embodiment,in which the bioactive composite is 70% by weight low molecular weightpolymer and 30% by weight bioactive glass (having a particle size of 90μm to 150 μm) the mean particle to particle distance may be betweenabout 100 μm to about 140 μm. Also within the scope of the presentinvention are bioactive composites comprising a gradient of bioactivematerial. For example, the gradient can vary along one or moredimensions. In another example, there may be greater concentrations ofbioactive material in one or more portions of the bioactive composite ascompared with other portions. Also envisioned are composites comprisinglayers of one or more types or concentrations of bioactive material, solong as at least one layer is in accordance with the invention.Structures prepared from such composites may have a bioactive portion ofthe composite at one or more specific locations, such that the bioactivematerial occurs where design specifications call for bone bonding. Inother embodiments, structures prepared using the composites of thepresent invention may have bioactive materials adhered to the surface.In further embodiments of the present invention, the structures may becoated with materials described and such coatings may be useful onmetallic, polymeric, or ceramic implants.

Bioactive composites and shaped bodies of the present invention madefrom the composites preferably demonstrate load-bearing and mechanicalproperties suitable for use in spinal, orthopaedic and dentalprocedures. Bioactive composites and shaped bodies of the presentinvention made from the composites also preferably demonstratebioactivity.

A formed bioactive composite material according to the present inventioncan be placed in or near bone to provide load-bearing stability andmicromechanical bonding to the bony material. After some time in thebody, the implanted material will begin to adhere to the bone tissueinterface, increasing the strength and toughness of the implant system.

It will be appreciated by those skilled in the art that the bioactivecomposites of the present invention may be used in a wide variety ofrestorative and surgical procedures including those involving bonetissues subject to large forces. One example is the repair or fusion ofvertebrae of the spine. Lower back pain may oftentimes be attributed tothe rupture or degeneration of lumbar intervertebral discs due todegenerative disc disease, ischemic spondylolisthesis, post laminectomysyndrome, deformative disorders, trauma, tumors and the like. This painmay result from the compression of spinal nerve roots by damaged discsbetween the vertebra, the collapse of the disc, and the resultingadverse effects of bearing the majority of the patient's body weightthrough a damaged unstable vertebral joint. To remedy this, spinalimplants may be inserted between the vertebral bodies to stabilize andsupport the joint and facilitate fusion via bone bonding. FIGS. 1-5 b,12-22 d, 53-57, 65-68 and 70 depict illustrative embodiments of spinalimplants comprising bioactive and biocompatible materials. The devicesof FIGS. 1-5 and 5 a-5 b for example, may be used in cervical fusionprocedures in which an anterior surgical approach is frequently used toplace the device between adjacent vertebrae; whereas the devices ofFIGS. 12-22 d for example, may be used in lumbar fusion procedures inwhich either an anterior or posterior surgical approach may be used.

Cervical Implants

The bioactive implant material may be formed into a variety of shapesfor use in bone implantation, such as spinal implantation or spinalfixation devices. In one embodiment, the implant material is preferablyformed into a cervical implant device.

FIGS. 1 through 4 illustrate various aspects of one embodiment of thecervical implant 10 of the present invention. Implant 10 may vary insize to accommodate differences in the patient's anatomy. The implant 10is comprised of an anterior side 60, a posterior side 70 opposing theanterior side 60, and a pair of opposing sidewalls 40. The anterior side60, the posterior side 70, and the sidewalls 40 are generally outwardlycurved in transverse cross-section. The curved sides are convex asviewed from the outside of the implant 10. The anterior side 60, theposterior side 70, and the sidewalls 40 join at points that generallydefine, in transverse cross section, a trapezoid. The transversecross-section, as used herein, is the plane perpendicular to the z-axis.As used herein, a trapezoid is a quadrilateral having two parallelsides, or any shape having the form of a trapezoid. The presentinvention employs geometric shapes to illustrate a preferred embodiment,but the present invention is not limited to such shape. Rather, thepresent invention broadly encompasses any variation in the claimedshapes within the spirit of the disclosure, including, for example,configurations in which gradually merge with adjacent sides andnon-uniform shapes that vary according to the transverse or longitudinalcross section.

The implant also comprises a top surface 20 and a bottom surface 30 thatis generally opposite the top surface 20. The top 20 and bottom surfaces30 can also be convex, or outwardly curved, in the longitudinalcross-section. The curvature and shape of each side grants the implantsuperior anatomical compatibility. The surfaces also maximize contactwith cortical bone to minimize subsidence of the implant into theendplates.

The top 20 and bottom 30 surfaces further include a plurality ofprojections 25, preferably wave-like or scalloped in shape (i.e.,pointed apex with rounded valleys), for gripping adjacent vertebrae. Thescalloped shape tooth design eliminates the stress concentrationtypically associated with other tooth designs and more evenlydistributes the compressive physiologic loads from the bone to theimplant. The projections 25 can be substantially uniform, upwardlyprotruding ribs. One skilled in the art would recognize theseprojections 25 as being substantially uniform, upwardly protruding,elongated ribs separated by concave channels. In alternativeembodiments, the projections 25 are randomly disposed or, in otherwords, situated in various directions. These projections 25 may also beupwardly protruding spikes. The wave-like shape of the projections 25increases the surface area of the implant for maximal vertebral contact.Further, the wave-like projections 25 provide significant resistance toexpulsion and retropulsion. In certain preferred embodiments, theprojections 25 have an angular pitch of between 1.75 degrees to 1.9degrees, a minimum depth of 0.022 inches, and an internal radius ofabout 0.022 inches. Other dimensional sizes of the projections 25 wouldnot depart from the present invention including upwardly protrudingspikes.

FIGS. 3a and 3b illustrate two alternative embodiments of the presentinvention. FIG. 3a illustrates implant 10 wherein the wall of theanterior 60 side has greater height than the wall of the posterior 70side. The implant 10 of FIG. 3a has a lordotic angle. FIG. 3billustrates implant 10 having no lordotic angle wherein the height ofthe wall for the anterior 60 side is equal to the wall height of theposterior 70 side. Due to the variety of machinations that may be usedto make the implants of the present invention, minute variations mayexist in the height of the anterior 60 and posterior 70 sides that wouldnot render them exactly the same height. Preferable lordotic angles fallin the range of about −20 degrees to about +20 degrees.

In FIG. 4, the implant 10 has a trapezoidal shape defined by thesidewalls 40, anterior 60, and posterior 70 sides. This shape maximizescontact with cortical bone. In preferred embodiments, the top 20 andbottom 30 surfaces are substantially identical in size and shape. Theshape also allows one skilled in the art to place graft material withina major recess 35 bordered by the sidewalls 40, anterior 60, andposterior 70 sides. This major recess 35 is formed in the body of theimplant and is in communication with at least one of the top or bottomsurfaces. A preferred embodiment has the major recess 35 having athrough-aperture that is in communication with both top 20 and bottom 30surfaces.

The implant also has a handling feature that may comprise at least onepair of elongated side recesses 43 and 53 for receiving forceps and afront recess 63 for receiving an impaction tool. “Recess,” as usedherein, describes a recessed indentation that generally defines adepression in a surface, for example, such as that defined as 43, 53,and 63 in FIGS. 1-3. The front recess 63 may be used in conjunction withthe anterior side 60 and front opening 65 as to communicate with animplant holder or insertion tool. The front recess 63 may be elongatedwith a major axis that is substantially transverse. The front recess 63may have an aperture, the front opening 65, formed therein. Thishandling feature allows for handling and insertion of the spinal implantusing instruments such as forceps. In some embodiments, the handlingfeature consists of only the front recess 63. In FIGS. 1 through 3, thesidewalls 40 further comprise side recesses 43 and 53 that may mate withan instrument to aid in insertion or removal of the implant. Thesidewalls 40 also comprise at least one opening 45 (FIGS. 1 and 3) toallow fluid to enter the major recess 35 after insertion. Graft materialmay be supplied with blood and other biologic fluids through theopenings 45. In other embodiments, the handling feature consists of onlythe side recesses 43 and 53. The surfaces of these recesses may betextured with an anti-skid material to prevent slippage of the insertiontool.

In FIGS. 1 and 2, the front recess is used to prevent rotation of theimplant. The front recess 63 and a front opening 65 can mate with animplant insertion tool. The front recess 63 may be comprised of someother geometry suitable to prevent the implant from rotating on the endof the implant insertion tool during insertion or removal of theimplant. In certain embodiments, the front opening 65 may be threaded tomate with a corresponding implant insertion tool. In other embodiments,the front recess 63 and/or the front opening 65 is eliminated.

FIG. 5 provides an exploded view of the bioactive composite implant 10showing an additional agent added to the composite implant—a graftmaterial 80 agent being placed in the major recess 35. Graft materialmay be comprised of allograft material, autograft material, or syntheticmaterials that have similar properties to allograft or autograftmaterials. The synthetic graft material is preferably comprised of abiocompatible, osteoconductive, osteoinductive, or osteogenic materialto facilitate the formation of a solid fusion column within thepatient's spine. One such example of such a synthetic graft material isVitoss® Bone Graft Substitute (available from Orthovita, Inc. ofMalvern, Pa.). To foster bone fusion, the Vitoss® calcium phosphatematerial may be saturated with the patient's own bone marrow aspirate,or therapeutic material such as growth factor, proteins, bone marrowaspirate, enzymes and other materials such as those disclosed in U.S.Pat. No. 7,045,125. Thus, the bioactive composite implant may haveincorporated therein or be in communication with other agents to aid infusion of adjacent vertebrae. It should be noted that in preferredembodiments, the posterior side 70 does not have an openingtherethrough. This facet of the design is a safety feature implementedto prevent leakage of graft materials placed in the major recess 35 intothe spinal canal.

FIGS. 5a and 5b show an alternate embodiment of a spinal implant.Similar to the implant of FIG. 1, the implant 10 a of FIGS. 5a and 5bhas a generally trapezoidal shape and a major recess having athrough-aperture that is in communication with both top and bottomsurfaces. The implant also has a handling feature that may comprise atleast one pair of elongated side recesses for receiving forceps and afront recess for receiving an insertion/impaction tool. The front recessmay be used in conjunction with the side recesses and/or front openingto communicate with an implant holder or insertion tool; however, unlikethe implant of FIG. 1, the implant of FIGS. 5a and 5b does not have sideopenings. The implant also includes a radiopaque agent—titanium markers800 a to provide the surgeon with radiopaque landmarks upon insertionand while the implant is in the body.

FIGS. 6 through 8 show a plate 90 and fastener 100 assembly that may beused in conjunction with implant 10. The plate and fastener assembly mayfacilitate fusion of adjacent vertebrae by stabilizing the implant inplace between the vertebrae. Fasteners 100 may be comprised of screws,pins, nails, and the like. They are inserted into openings within plate90 to engage the adjoining vertebral bodies. Upon insertion, one pair offasteners is inserted in the upper vertebral body and one pair isinserted in the lower vertebral body.

FIGS. 9 through 11 show accessories 110 and 120 that are used to connectone or more implants 10 as shown in FIG. 11. Accessories 110 and 120 maybe used in corpectomy procedures in which the surgeon removes one ormore vertebrae and needs to restore the spine to its former height. InFIG. 9, accessory 110 has two male ends that may engage, for example,the major recess 35 of implant 10 or the female end of accessory 120. InFIG. 10, accessory 120 has a male end 123 and a female end that allowsimplants to be joined together as shown in FIG. 11. Accessories 110 and120 may be joined together with implants 10 via snap or compression fitvia one or more flexible tabs, fasteners, adhesives, or other means.

Trial instrument kits may be used with the present invention spinalimplant to aid in determining proper sizing of the final implant foreach individual patient. Non-limiting examples of such kits includeSpinal Elements® Crystal® Cervical Cage System and Crystal® Instruments.

Anterior Lumbar Interbody Fusion (ALIF) Implants

The bioactive material of the present invention may also be formed intoan implant suitable for ALIF procedures. ALIF implant devices aregenerally suitable for implantation in the lumbar regions of the spine.

FIGS. 12 through 14 depict one embodiment of the ALIF implant 130 of thepresent invention. Like the cervical implant of the present invention,implant 130 may be in a variety of different sizes to accommodatedifferences in the patient's anatomy or the location of the spine thatimplant 130 will be inserted. The body may substantially form an ovalshape in the longitudinal cross-section. The implant is a bodycomprising a bioactive substance and further comprising: an anteriorside 180, a posterior side 190 opposing the anterior side 180, and apair of opposing sidewalls 160, said sidewalls 160 being generallyoutwardly curved or generally “c-shaped.” The anterior 180 and posterior190 sides may be parallel and in others they are outwardly curved. Theimplant also has a top surface 140 and a bottom surface 150, bothsurfaces coupled with the sidewalls 160. Top surface 140 and the bottomsurface 150 form plural projections 145 for enhancing interaction with asynthetic or natural vertebral body. At least one major recess 135 isformed in the body in communication with at least one of the top surface140 and the bottom surface 150.

Also in FIGS. 12 and 14, top 140 and bottom 150 surfaces further includea plurality of projections 145, preferably wave-like or scalloped inshape, for gripping adjacent vertebrae. These projections share the samecharacteristics of the plurality of projections 25 noted in thedescription of the cervical implant.

FIG. 14 illustrates one embodiment of the present invention. FIG. 14illustrates implant 130 having a lordotic angle: The lordotic angle canrange from −20 degrees to +20 degrees.

Similar to the cervical implant 10, the ALIF implant has a major recess135 that forms a through-aperture. This shape maximizes contact with thecortical bone in the thoracic and lumbar regions. In preferredembodiments, the top 140 and bottom 150 surfaces are substantiallyidentical in size and shape. The major recess 135 also maximizes thechances of fusion because an additional agent-graft or resorbablematerial may be packed within implant 10. It should be noted that inpreferred embodiments, posterior side 190 does not have an openingtherethrough. This is to prevent leakage of graft materials from themajor recess 135 into the spinal canal.

The implant also has a handling feature comprising recesses 147 and 157along the top 140 and bottom 150 surfaces extending from either theanterior 180 and posterior 190 sides that act as guide rails and atleast one recess 185 in the anterior or sidewalls 160 for receiving animpaction tool. FIGS. 12 and 13 show the recesses 147 and 157 that actas guide rails. The guide rails mate with an instrument, such as aparallel distraction instrument, to aid in insertion or removal of theimplant. The plurality of guide rails holds the implant securely and mayallow the surgeon to insert the implant more evenly.

FIG. 12, shows the implant 130 having a front recess 183 used as ananti-rotation recess and a front opening 185. The front recess 183 andopening 185 share the same characteristics as the front recess 63 andfront opening 65 of the cervical implant described earlier.

FIG. 15 provides an isometric view of an alternative embodiment 200 ofthe ALIF implant of the present invention. Implant 200 includes a strut210 that divides the major recess 135 into two through-apertures toprovide support during anterior impaction of the implant duringinsertion. A strut 210 that has the top 140 and bottom 150 surfaces withprojections 145 separates the through-apertures.

FIGS. 16 through 19 provides yet another embodiment of the presentinvention in which an ALIF implant 215 or implant 200 further includes afastening feature. The fastening feature comprises at least onethrough-aperture 220 in communication with the anterior 180 side andeither the top 140 or bottom 150 surface for insertion of fasteners 230that communicate with a synthetic or natural vertebral body either belowor above the implant. This feature includes a plurality of openings 220on the anterior side of implant 200 for receiving fasteners 230.Fasteners 230 may include, but are not limited to, screws, pins, nails,or any other fixation devices. In certain preferred embodiments,openings 220 are angled to allow fasteners 230 to move at varying anglesup and in or down and in. An angle in some embodiments that may bepreferred is below about 90 degrees. In others, and angle of about 45degrees may be preferred. Fasteners 230 help to anchor implant 215 sincethe upward tilted fastener is inserted into the upper vertebral body andthe downward tilted fastener is inserted into the lower vertebral body.

Posterior Lumbar Interbody Fusion (PLIF) Implants

The bioactive material of the present invention may also be formed intoan implant suitable as for PLIF procedures. PLIF implant devices aregenerally suitable for implantation in the lumbar regions of the spine.

The PLIF implant 240 of the present invention may be in a variety ofdifferent sizes to accommodate differences in the patient's anatomy orthe location in the spine. As FIGS. 20 through 22 illustrate, implant240 comprises an anterior side 290 and a posterior side 300 beingparallel to and opposing the anterior side 290; a lateral 280 side and amedial 270 side with one side being outwardly curved and the other beinginwardly curved; and a top surface 250 and a bottom surface 260, each ofthe top 250 and bottom surfaces 260 including plural projections 255 forenhancing interaction with a synthetic or natural vertebral body. Theprojections 255 are similar in geometry to the protrusions in thecervical and ALIF implants of the present invention.

The implant also comprises a major recess 245 formed in the bodycreating a longitudinal through-aperture in communication with the top250 and bottom 260 surfaces, at least one minor recess 275 formed in thebody creating a latitudinal through-aperture in communication with thelateral 280 and medial 270 sides, both through apertures incommunication with each other. The convergence of thesethrough-apertures forms a cavity inside the implant in which graftmaterial may be placed. This cavity formed by the through-aperturespromotes bone growth and fusion between the adjoining vertebral bodies.Opening 245 may be packed with graft material to promote bone growth andfusion. Graft materials suitable for this purpose includes any of thematerials disclosed herein. Blood and other biological fluids can beprovided to the graft material through the minor recess 275.

The implant also comprises a handling feature comprising a pair ofanterior recesses 273 formed at points where the anterior 290 sidecommunicates with the lateral 280 and medial 270 sides. The anteriorrecesses 273 are used for receiving a manipulator. There are also a pairof posterior recess 283 formed at points where the posterior 300 sidecommunicates with the lateral 280 and medial 270 sides. The handlingfeature also includes a front opening 295 formed in the anterior 290side. The handling feature facilitates the handling and insertion of thespinal implant into an intervertebral space.

FIGS. 20 and 22 illustrate implant 240 having a lordotic angle. Thelordotic angle can range from −20 degrees to +20 degrees. In otherembodiments, anterior side 300 and posterior side 290 are of the sameheight and have no lordotic angle.

In FIGS. 20 through 22, the anterior recesses 273 and the posterior 283recesses may mate with an instrument, such as forceps, to add in theinsertion or removal of the implant. The front 295 and rear openings 305also allow implant 280 to be gripped and mated with an insertion tool.In certain embodiments, the medial 270 and lateral 280 sides may furthercomprise at least one minor recess 275 (or 285) to allow fluid to enterthe interior of the implant after insertion.

Implant 240 may further include an opening 295 in posterior side 300,that is preferably internally threaded to accommodate an insertion tool,but that does not completely extend through the thickness of theposterior wall. This facet of the design is a safety feature implementedto prevent leakage of graft materials and the like, that may be placedin the hollow interior of the implant, into the spinal canal.

Implant 240 may be used alone or in conjunction with a complimentaryimplant. The two implants can be placed along side one another as in amirror image with the medial 270 sides facing one another. Thisconfiguration allows bone graft material to be placed between twoimplants 240 and provides for maximum contact between natural bone andthe implants.

Transforaminal Lumbar Interbody Fusion (TLIF) Implants

The bioactive material of the present invention may also be formed intoan implant (FIGS. 22a-22d ) suitable for TLIF procedures. TLIF implantdevices are generally suitable for implantation in the lumbar regions ofthe spine.

In another embodiment of the present invention (FIG. 22a ), the TLIFimplant x1 of the present invention may be in a variety of differentsizes to accommodate differences in patient's anatomy or the location ofthe spine that the implant x1 will be inserted. The TLIF implant x1 maybe a variety of different sizes to accommodate differences in thepatient's anatomy or the location in the spine. As FIGS. 22a through 22dillustrate, implant x1 comprises an anterior side x6 and a posteriorside x7 being parallel to and opposing the anterior side x6 and alateral x8 side and a medial x9 side with at least one side beingoutwardly curved. The implant also comprises a top surface x2 and abottom surface x3, each of the top x2 and bottom surfaces x3 includingplural projections x4 for enhancing interaction with a synthetic ornatural vertebral body. Wave-like projections x4 are similar to thecervical, ALIF, and PLIF implants of the present invention.

Top surface and bottom surface x2 and x3 further define at least onemajor recess x5 to promote bone growth and fusion between the adjoiningvertebral bodies. The major recess x5 creates a longitudinalthrough-aperture in communication with the top x2 and bottom x3surfaces. The major recess x5 may be packed with graft material tofurther promote bone growth and fusion. Graft materials suitable forthis purpose includes any of the materials disclosed herein.

As FIGS. 22a through 22d illustrate, the anterior x6 and posterior x7sides are generally flat and parallel. In certain preferred embodiments,the lateral x8 side is outwardly curved and the medial x9 side isinwardly curved.

The implant also comprises a handling feature comprising a pair ofanterior recesses x11 formed at points where the anterior x6 sidecommunicates with the lateral x8 and medial x9 sides and a pair ofposterior recess x10 formed at points where the posterior x7 sidecommunicates with the lateral x8 and medial x9 sides. The pairs ofrecesses (x10 and x11) may be used for communication with a manipulatoror instrument, such as, forceps. The handling feature also includes afront opening x14 formed in the anterior x6 side and a rear openingformed in the posterior x7 side both communicating with athrough-aperture. This through-aperture is also in communication withthe cavity formed in the spinal implant by the longitudinal andlatitudinal through-apertures. The handling feature facilitates thehandling and insertion of the spinal implant into an intervertebralspace.

In certain embodiments (FIG. 22c ), lateral x8 and medial x9 sides mayfurther comprise at least one opening x12 and x13 to allow fluid toenter the interior of the implant after insertion to provide graftmaterial placed in the center of the implant with blood or otherbiological fluids. FIGS. 22c and 22d show an embodiment of the implantwith two side openings x12 and x13 per wall. However, it should beunderstood that the implant may not have side openings, or may havemultiple pinhole openings along the length.

Implant x1 may further include an opening x14 in both of the anterior x6and posterior x7 sides that may be internally threaded to accommodate aninsertion tool. The front recess x14 may have an internal taper to matewith a tapered insertion instrument.

As shown in FIG. 22c , the top and bottom surfaces and may be outwardlycurved. Further, the implant may be wedge shaped such that there is alordotic angle. The lordotic angle may be same as those describedearlier in other embodiments of the invention. In some embodiments theheight of the wall of the anterior side x6 is greater than the height ofthe wall of the posterior side x7. Alternatively, the height of thesewalls may be equal.

The TLIF implant of the present invention is designed to engage thecortical rim of the vertebrae, the strongest portion of the vertebrae,and, as such, increases biomechanical stability. Additionally, theplacement of this type of implant is generally less invasive and lessdestructive than other procedures, and may be cost effective since onlyone implant is used.

Surgical Instrumentation

The present invention also provides surgical instrumentation to aid inthe insertion, placement, or removal of the implants of the presentinvention.

FIGS. 23 through 27 illustrate various aspects of the paralleldistraction instrument 310 of the present invention. Paralleldistraction instrument 310 is suitable for the insertion of the ALIFimplant of the present invention. The instrument 310 includes a pair ofupper 320 and lower 330 forks that mate with the guide rails of the ALIFimplant. For example, FIGS. 23 and 24 show instrument 310 engagingimplant 130 via upper fork 320 engaging guide rails 147 on the topsurface 140 of implant 130 and lower fork 330 engaging guide rails 157on the bottom surface 150 of implant 130. Once instrument 310 holds theimplant securely in place, the surgeon can insert the implant into theintervertebral space. Upon insertion of the instrument 310 with theimplant, the handle 340 (see FIG. 27) of instrument 310 is depressed toactuate the two pairs of forks 320 and 330 in a parallel manner. In analternate embodiment, a further insertion tool may slide betweeninstrument 310 to place the implant in the intervertebral space.Instrument 310 further includes a scissor hinge and ratchet catch toallow for faster actuation than traditional screw style stops of theprior art and a faster release. Once instrument 310 is actuated, adevice of the type shown in FIGS. 28-32 can pass through forks 320 and330 and screw into opening 185 of the implant.

FIGS. 28 through 31 illustrate various features of an implant insertionand impactor tool 350. The tool 350 may be suitable for the insertion orremoval of the cervical, ALIF, and PLIF implants of the presentinvention. Accordingly, the dimensions of tool 350 may vary dependingupon the implant being inserted. Tool 350 includes a tip 360 that iscomprised of a shock absorbing material that can withstand impact, suchas a RADEL® tip and a sturdy body comprised of a material such as metaland a gripping handle 353. Tip 360 can be modular so that it isremovable from the body of tool 350. Tip 360 has a projection 363 thatmates with the anti-rotation convexity of the implant. The tip 360further includes at least one opening 365, preferably a central openingthat allows a “guide wire” with a threaded tip 370 to advance. Incertain embodiments, threaded tip 370 advances through opening 365 uponrotation of the advancer 380 adjacent to the tool handle 353 (see FIGS.28 and 30). Both the threaded tip 370 and projection 363 on the tool tip360 mate with the threaded opening and anti-rotation convexity of theimplant to allow for insertion or removal of the implant.

FIG. 31a shows an isometric view of another embodiment of the implantinsertion tool 350 featuring a threaded tip that can be advanced viaeither rotation of the advancer 380 or of the rotatable end knob 380 a.

FIGS. 32 through 34 illustrate various features of another embodiment ofan insertion and impaction tool 390 of the present invention. Tool 390mates flushly with the implant face and allows for impaction at theopposite end of the tip. Similar to tool 350, tool 390 has a tip 400that is comprised of a shock absorbing material such as RADEL® and asturdy body which is comprised of a metal and a gripping handle. Tip 400has a projection 403 that mates with the anti-rotation convexity of theimplant. Tip 400 may further include at least one opening 405,preferably a central opening, that allows a “guide wire” with a threadedtip to advance.

FIG. 35 illustrates an alternate embodiment of the implant insertion andimpaction tool 410 of FIG. 30 that includes a limiting impaction tip420. Limiting impaction tip 420 has stops 430 that allow the surgeon togauge how far tip 420 and the implant is displaced in the anterior toposterior direction with respect to the vertebral bodies. The height ofstops 430 in a vertical direction may be any height that prevents tool410 from going in-between adjacent vertebral bodies. The limitingimpaction tip 420 may be modular or removable from tool 410. Tip 420 maybe made with a set stop length that ranges between about 2 mm to about 4mm to allow the surgeon to gauge how far into the intervertebral spacethe implant is being inserted.

FIGS. 36 through 39 illustrate various aspects of forceps 440 of thepresent invention that may be used for insertion of implants, such asthe cervical implants 10 of the present invention. Forceps 440 may beused to as an alternative to the insertion and impaction tools 350 and390 of the present invention. Forceps 440 are generally scissor-like inshape and have two openings at the handle to accommodate the fingers ofthe surgeon. Forceps 440 may include nubs 450 on the inside of each tip445 for mating with the openings on the medial and lateral sides of theimplant 10. Tip 445 may further include shock absorbing pads 460 thatare comprised of a material such as RADEL® to cushion the implant if theforceps 440 are also used for impaction.

FIGS. 40 and 41 provide an exploded and isometric view of an insertionand impaction tool 470 that is suitable for use with any of the implantsof the present invention. Tool 470 may be provided with a modular tip480 that may be made of a shock absorbing material, such as but notlimited to RADEL®, that is secured to tool 470 with a fastener 490 orother means. This allows tip 480 to be replaced after wear due torepeated use. Alternatively, the insertion and impaction tool may beintegral with the tool body and handle such as tool 500 in FIG. 42.Preferably the tip of tool 470 or 500 is rounded and smooth-edged. Inuse, the impactor and insertion tool 500 is placed flush against theimplant 10 (see FIG. 43) and then tapped via impaction hammer 510 toadjust the position of the implant (see FIGS. 44 through 47 c). Theimpaction and insertion tool allows for the surgeon to focus on variouscontact spots such as the medial aspect, the lateral aspect or thecenter of the implant for medial, lateral, and the anterior to posteriorpositioning of the implant (see FIGS. 45 through 47 c).

FIG. 47d shows a side view of a rasp y1 of the present invention used inthe preparation of the endplate. The rasp y1 is in the shape of theimplant being inserted so as to contour the endplates to accommodate theeventual implant being inserted and provide for good contact between theendplate bone and the implant. Although FIG. 47d shows a rasp y1 with aheadpiece y2 in the shape of a cervical type implant, it should beunderstood that the headpiece y2 of the rasp y1 could be in any implantshape including the ALIF, PLIF and TLIF types disclosed herein. Rasp y1also includes a handle y3, which may be integral to or a modular withthe headpiece y2, for gripping and manipulating the rasp y1. FIGS. 48and 49 provide an isometric and detailed isometric view of trial tools520 with plugs 530 of the present invention. Tool 520 is used afterpreparation of the intervertebral space and prior to insertion of theimplant to determine the size of the implant to insert. Plugs 530 can bemodular (i.e., fasten or snap onto the end of tool 520) or be integratedinto tool 520. Plugs 530 are generally the same size and shape of theimplant. In FIG. 49, plug 530 may be similar in size and shape to thecervical implant 10 of the present invention.

FIGS. 50 through 52 illustrate various aspects of the view of graftimpaction block and implant/tool holder 540 of the present invention.Graft impact block 540 comprises a plurality of recesses 550 of varioussizes to accommodate various sizes of implants of the present invention.Block 540 allows other agents-such as graft material to be packed intothe hollow interior of the implant.

FIG. 53 depicts another embodiment of a spinal implant made from thematerial of the present invention showing the flexibility of thebioactive composite material to be machined or molded into an intricatedesign.

FIG. 54 is an example of another embodiment of a vertebral body spinalimplant made from the material of the present invention and including agraft material in the center of the implant. In this embodiment, thecomposite ring has a first portion 210 a comprised of the bioactivecomposite material (e.g., biocompatible polymer and bioactive glass) ofthe present invention and a second portion 212 a comprised of anadditional material, preferably a porous, inorganic calcium phosphateagent.

FIG. 55, FIG. 56, FIG. 57 show various bone dowels for spinal fusion inplace in the vertebral body (vertebral body shown in phantom). The bonedowel of FIG. 55 has a plurality of ports, some of which are shown 224a. Hardenable material such as bone augmentation materials and bonecement may be injected into the dowel, emerging from the ports topartially surround the dowel 228 a. FIG. 56 depicts another bone dowelfor spinal fusion. The end of an injection device or syringe 226 a isshown. Bone augmentation material 224 a is shown emerging from accessports 228 a in the dowel.

Bone Repair

In other embodiments of the present invention, the composite shaped bodymay be used in a variety of orthopaedic procedures involving bone repairand restoration. Long bones are comprised of the both cortical andcancellous (metaphyseal) bone. The present invention composite may beformed into a cortical bone sleeve via machining or other means.Orthopaedic appliances such as joints, rods, pins, suture fasteners,anchors, repair devices, rivets, staples, tacks, orthopaedic screws andinterference screws, and a number of other shapes may be formed from thebioactive composite material in and of itself or used in conjunctionwith conventional appliances that are known in the art. Such bioactive,composite shaped bodies can be used in conjunction with biocompatiblegels, pastes, cements or fluids and surgical techniques that are knownin the art. Thus, a screw or pin comprised of the present inventionbioactive composite material can be inserted into a broken bone in thesame way that metal or polymeric screws and pins are currently inserted.The bioactivity of the material will give rise to osteogenesis withbeneficial medical or surgical results.

The bioactive composite material of the present invention may also beshaped into other orthopaedic devices including, but not limited to,sheets, bone plates and bone plating systems, bone scaffolds, bone graftsubstitutes, bone dowels and other devices useful in fixing bone damagedby, for example, trauma or surgery.

In some aspects of the present invention, the composite shaped body maybe used in orthopaedic procedures such as total hip arthroplasty andfracture fixation. Total hip arthroplasty is a surgical procedure inwhich the hip joint is replaced by a prosthetic. Such joint replacementsurgery generally is conducted to relieve arthritis pain or fix severephysical joint damage as part of hip fracture treatment. The hip jointcomprises the femur and acetabulum. The femur terminates at the proximalend in a femoral head of generally spherical shape. The acetabulumcooperates with the femur by serving as a cavity that allows forarticulation with the femoral head. With a hip implant, the femoral headis excised or resected to expose the femoral intramedullary canal. Thestem of the hip implant is surgically implanted within the femoralintramedullary canal for fixation thereto either by bone cement, boneaugmentation material or by a press fit. The proximal end of the hipimplant terminates in a spherical head. A cup assembly is carried on thespherical head for engagement and articulation with the acetabulum. FIG.58 depicts an illustrative embodiment of an orthopaedic hip implantcomprising the bioactive and biocompatible materials of the presentinvention. The implant may in part or whole be comprised of thecomposite.

FIGS. 59a and 59b depict insertion of femoral hip dowels 330 a into afemur, shown in phantom, requiring restoration. Access ports 332 apermit the injection of hardenable material, such as bone augmentationmaterial or bone cement, into the dowel and, via the ports, around thedowel to effect fixation in the femur head. FIGS. 60a through d aredifferent forms of dowels 330 a of the type useful for hip or otherreconstruction. Optional access ports 332 a are present in FIGS. 60b and60 d.

FIGS. 61a and 61b depict the use of the present invention material as areceptacle sleeve 100 a that is inserted into the body to facilitate abipolar hip replacement. Cavity 102 a is machined into the sleeve 100 ato accommodate the insertion of a ball joint implant or prosthesis 103a. An orthopaedic surgeon drills a cavity or furrow into the bone 101 ato receive sleeve 100 a. Sleeve 100 a is then affixed to the surroundingbone via a bone augmentation material or bone cement layer 104 a orother means. On the acetabular side, a femoral head articulation surface106 a is maintained within a prepared cavity via the material of thepresent invention 100 a and a bone cement layer. A high molecular weightpolyethylene cup or cup of similar type material, 105 a is used tofacilitate articulation with the head of the prosthesis 103 a. The balljoint implant or prosthesis 103 a is thus inserted into a cup 105 a tofacilitate joint movement.

FIG. 62 shows the material within a human femur that is used as a block92 a for bulk restoration or repair of bulk defects in bone or oncologydefects, or as a sleeve 94 a for an orthopaedic screw, rod or pin 98 aaugmentation. Item 99 a depicts an orthopaedic plate anchored by theorthopaedic device item 98 a. Bone cement layer 96 a surrounds andsupports sleeve 94 a in place. These screw, rod and plate devices may bemade of medical grade metal or other material, or may be comprised ofthe bioactive composite material of the present invention. For instance,FIG. 63 depicts an illustrative embodiments of such bone screwscomprising the bioactive and biocompatible materials of the presentinvention; and FIG. 64 depicts an illustrative embodiments of such boneplates comprising the bioactive and biocompatible materials of thepresent invention.

FIGS. 65a through c depict other synthetic cortical vertebral spacer orinterbody device embodiments. Hard material, 240 a preferably compositematerial in accordance with the invention, forms the spacers and rings.In some embodiments a plurality of regions form the shaped body asillustrated in FIG. 65c . The present invention bioactive compositematerial 240 a forms an outer portion of the ring, while a porous agent,especially a porous calcium phosphate material 242 a forms an innerportion of the body.

FIGS. 66a through c depict still other embodiments of synthetic corticalbone dowels or interbody devices 250 a. The dowels may have access ports252 a for emergence of hardenable material when such material isinjected into orifice 254 a with a syringe device. The dowels anddevices may be composite materials as set forth herein. FIG. 67 isanother form of cortical spacer. The spacer has a relatively hard outerportion 260 a formed of the present invention bioactive compositematerial along with a calcium phosphate derived (or similar agent) innerportion 262 a.

FIG. 68 is a synthetic cortical vertebral interbody device of anotherform.

FIG. 69 depicts a synthetic cortico-cancellous defect filling form forbone restoration. The bioactive composite of the present invention 270 ais combined with a calcium phosphate based portion or other similar typeof osteoinductive agent 272 a to give rise to another embodiment of abioactive, composite shaped body.

FIG. 70 is a synthetic cortical ring. The bioactive composite of thepresent invention may have a central opening or the opening may befilled, e.g. with bone graft substitutes or osteoinductive agents. Thering may also have an inner portion formed from another agent.

FIG. 71 shows a synthetic cortical rod comprised of the bioactivecomposite material of the present invention for orthopaedic restoration.

FIG. 72a shows the present invention material prepared in accordancewith an embodiment of the present invention, which is machined or moldedto patient specific dimensions. FIG. 72b depicts the use of the materialthat is formed into the shape of craniomaxillofacial implant 76 a, azygomatic reconstruction 72 a, or a mandibular implant 74 a.

FIG. 73a depicts a plug 80 a of the present invention material. FIG. 73billustrates the plug 80 a which is inserted into an excavation site 83 awithin a human knee, below the femur 81 a and above the tibia 82 a, foruse in a tibial plateau reconstruction. Plug 80 a is held in place orstabilized via a bone cement layer 84 a.

Dental Implants

The bioactive composite may also be formed into the shape of acraniomaxillofacial implant or may find particular utility in a varietyof dental procedures including use as a dental implant. Dental implants1000 may be placed into either the maxilla or mandible to form astructural and functional connection between the living bone (FIG. 74).

FIG. 75a shows the material of the present invention formed into theshape of a sleeve 60 a. Item 62 a depicts the excavated cavity which canbe formed via machining or other means. Item 64 a presents a pluralityof threads which can be coated with bone cement or a variety ofosteoinductive and/or osteoinductive materials. FIG. 75b shows thesleeve 60 a inserted into the jaw bone 66 a and gum 67 a. The sleeve 60a may be fixed in place via pins, bone cement, or other mechanical meansof adhesion. An artificial tooth or dental implant 68 a can then bescrewed into sleeve 60 a by engaging threads 64 a.

The shaped bodies can be modified in a number of ways to increase ordecrease their physical strength and other properties so as to lendthose bodies to still further modes of employment. Overall, the presentinvention is extraordinarily broad in that shaped bodies may be formedeasily, under carefully controllable conditions, and with enormousflexibility. In conjunction with certain embodiments of the presentinvention, shaping techniques are employed on the bioactive compositeshaped bodies of the present invention. Thus, such bodies may bemachined, pressed, stamped, drilled, lathed, or otherwise mechanicallytreated to adopt a particular shape both externally and internally.Preformed shapes may be formed in accordance with the invention fromwhich shapes may be cut or formed. For example, an orthopaedic sleevefor a bone screw may be machined from a block of material made hereby,and the same tapped for screw threads or the like.

In addition to the shaped implants described above, certain aspects ofthe present invention provide for kits that contain sterile shapedimplants within sterile packaging alongside appropriate instrumentationfor inserting or implanting the shaped implant.

Throughout this disclosure, various aspects of the invention arepresented in a range format. It should be understood that thedescription in range format is merely for convenience and brevity andshould not be construed as an inflexible limitation on the scope of theinvention. Accordingly, the description of a range should be consideredto have specifically disclosed all the possible subranges as well asindividual numerical values within that range. For example, descriptionof a range such as from 1 to 6 should be considered to have specificallydisclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numberswithin that range, for example, 1, 2, 2.3, 3, 4, 5, 5.7 and 6. Thisapplies regardless of the breadth of the range.

EXAMPLES

Additional objects, advantages, and novel features of this inventionwill become apparent to those skilled in the art upon examination of thefollowing examples of the invention. The examples are included to moreclearly demonstrate the overall nature of the invention. The examplesare exemplary, not restrictive, of the invention.

Bioactivity

Samples were mixed in a solid state, without the addition of a solvent.The materials were dry mixed thoroughly by tumbling on rollers for abouttwo hours until a homogeneous mixture was observed. The mixed compositewas added to a barrel and plunger extruder set to an adequatetemperature to melt the polymer. The barrel and plunger extruder wasused to fill a pre-heated disc mold. The molded sample was removed and ahole-saw was used to core out a smaller circular-disc sample. Thissample was then milled on the top and bottom to further expose thebioactive glass.

Molded samples were made from various composites of PEEK and Combeitebioactive glass-ceramic at various particle sizes according to theprocess described above. Both discs (diameter=12 mm) and cylinders(diameter=5-6.5 mm) were used for testing. The samples were suspended insimulated body fluid at 37° C. for 3, 7, 14, 21, and 28 days.

Referring to FIGS. 76-83, composites comprising PEEK and varying weightpercentages of Combeite glass-ceramic (having <53 micron averageparticle size) were prepared using the methods set forth. In vitrobioactivity studies were performed with the composites, prepared asdescribed, using the method of Kokubo, How useful is SBF in predictingin vivo bone bioactivity, Biomaterials (2006) 27:2907-2915. Afterimmersion in SBF for 3 days, the formation of a significant amount ofcalcium phosphate can be observed for the 60% by weight PEEK and 40% byweight Combeite (60/40) sample and formation of calcium phosphate can beseen in the 70% by weight PEEK and 30% by weight Combeite (70/30) sample(FIG. 77). Referring to FIGS. 78-80, the development of increasingamounts of the calcium phosphate for each of the samples can be observedover time; the amount of Combeite bioactive glass-ceramic in the sampleproportionally influences the rate at which the calcium phosphate forms.FIG. 82 shows that, after 28 days, a significant amount of calciumphosphate forms on the 80% by weight PEEK and 20% by weight Combeite(80/20) sample and is beginning to form on the 90% by weight PEEK and10% by weight Combeite (90/10) sample. FIG. 81 shows a cross-section ofthe bioactive layer of the 60/40 sample after 21 days along with anatomic analysis of the layers. FIG. 81 also shows the significance ofthe interface of the bioactive glass and its relation to the bioactivelayer. By comparison, a sample of 100% PEEK, without the bioactivecomponent, does not result in the formation of calcium phosphate (FIGS.76-78).

Also by comparison, FIG. 83 shows the development of calcium phosphateover a 14 day period on samples of PEEK and Combeite, for which theaverage particle size of the Combeite is about 90 to 150 μm. ComparingFIG. 83 with FIG. 79, it is evident that a significant amount of calciumphosphate has developed on the 90/10 sample (90 to 150 μm) after 14days, but no calcium phosphate developed on the 90/10 (<53 μm) sampleover the same period of time. This suggests that bioactivity may betailored by altering the size of the bioactive glass.

Composite shaped bodies were manufactured according to the preferredmethod of the present invention. PEEK polymer and Combeite bioactiveglass (90-150 μm) were compounded into pellets using a twin screw, dualhopper extruder. The resultant composite pellets were then injectionmolded into near net shape articles and further machined to produceshaped spinal implants. FIGS. 84 and 85 display the in vitro bioactivityof two exemplary embodiments of the composite shaped spinal implantafter immersion in simulated body fluid for a period of 7 days.

Mechanical Testing

Samples were made with varying grades of PEEK and Combeite bioactiveglass and subjected to a host of tests to evaluate the mechanicalproperties of the samples. These samples were compounded by preblending(dry), adding to a single hopper, and melt mixing in a single screwextruder (Quad die opening; 5 zone 2.5″; single hopper pre-blend; waterspritz; air knife, pelletizer; classifier). Resultant composite pelletswere then injection molded to standardized shapes for testing (55 TonBengel Injection molder; 3-Up family mold for tensile and flexuralsamples (flexural samples cut in half for Izod impact testing). Table 2displays the mechanical properties of various materials manufactured inaccordance with the single hopper/single screw processing method of thepresent invention.

TABLE 2 Compressive Compressive Flexural Flexural Impact StrengthModulus Strength Modulus Strength Formulation (MPa) (GPa) (MPa) (GPa)(kJ/m{circumflex over ( )}2) 80/20 450G 110-130 3.5-4.5 165-175 5.9-6.27.7 (90-150 μm) 70/30 450G 115-130 3.5-4.5 165-170 6.7-6.9 8.0 (90-150μm) 60/40 150G 115-135 4.5-5.0 145-165 8.1-8.2 4.8 (<90 μm) Victrex 120165 4.1 8 450G* Victrex 120 175 3.9 5 150G* *published values

Additional samples were compounded into composite pellets by FosterCorporation using a 30-40 mm twin screw extruder with a dual hopper feedsystem. The resultant composite pellets were then injection molded bySpectrum to standardized shapes for testing using a 50-80 ton hydraulicinjection molding machine. Table 3 displays the mechanical properties of80/20 material manufactured in accordance with the twin screw/dualhopper processing method of the present invention in comparison to 100%PEEK (450G).

TABLE 3 Impact Strength Tensile Comp Comp Flex Flex (kJ/m2) TensileElong Tensile Strength Modulus Strength Modulus complete Strength @break Modulus Composition (MPa) (MPa) (MPa) (MPa) (hinged) (MPa) (%)(MPa) 80/20 128 3077 169 5189 5.5 (6.6) 86 19 5371 (90-150 μm) 450GVictrex 450G* 120 165 4100 8 100 45 *published valuesDynamic axial fatigue testing of PEEK/Combeite spinal implant sampleswas also conducted. The spinal implants were comprised of the bioactivecomposite material of the present invention (low molecular weight 70/30(90-150 μm glass) material), similar in design to the implant shown inFIG. 5a with a lordotic angle of 7 degrees (anterior to posterior). Thepurpose of this test is to determine the ability of the material tohandle repeated cycles of loading and unloading in a simulated in vivoenvironment. Testing was conducted at 37° C. in phosphate bufferedsaline (PBS) (e.g., under simulated in vivo conditions). The implant wascapable of withstanding 5 million cycles at an applied load of 2000Newtons (N) with no observed failure. The results show that thecomposite material of the present invention can withstand many cycles ofloading and unloading as is typically experienced in clinical use.

Melt Flow Rate

The melt flow rate (MFR) of various bioactive composite materialsmanufactured in accordance with the methods of the present invention atvarious compounding facilities were measured using an extrusionplastometer, following the methods of ASTM D1238-04c (Procedure A).These results are displayed in Table 5 in relation to the melt flowrates of the 100% PEEK polymer materials (LT1, 450G, LT3, 150G). Theseresults show that as the percentage of bioactive glass is increased, themelt flow rate of the resultant composite material is appreciablydecreased.

TABLE 5 Melt Flow Rate Measurement Description (g/10 min) Time (sec)100% LT1 Medical Grade PEEK (high 2 60 molecular weight PEEK) 100% 450GTechnical Grade PEEK (high 2 60 molecular weight PEEK) 80/20(450G/90-150 μm) Twin Screw 0.59 60 Compounded at Foster 80/20(450G/90-150 μm) Twin Screw 0.94 180 Compounded at Polymers Center 80/20(450G/90-150 μm) Single Screw 0.08 300 Compounded at Infinity 70/30(450G/90-150 μm) Twin Screw 0.067 600 Compounded at Foster 80/20(LT1/<53 μm) Twin Screw 0.12 300 Compounded at Polymers Center 80/20(450G/<53 μm) Twin Screw 0.1 300 Compounded at Polymers Center 100% LT3Medical Grade PEEK (low 18 60 molecular weight PEEK) 100% 150G TechnicalGrade PEEK (low 24 60 molecular weight PEEK) 77/23 (LT3/90-150 μm) TwinScrew 13 60 Compounded at Foster 70/30 (150G/90-150 μm μm) Single Screw2.7 60 Compounded at Infinity 60/40 (150G/<90) Twin Screw 1.2 180Compounded at Polymers Center “Foster”—Foster West Corporation, NorthLas Vegas, NV “Infinity”—Infinity Compounding, Logan, NJ “PolymerCenter”—Polymers Center of Excellence, Charlotte, NC

Homogeneity

The ash content of various formulations manufactured (at multiplecompounding facilities) according to the methods of the presentinvention was measured according to a modified ASTM D5630-06 procedureB. Two grams of composite pelletized material was burned off at 900 Cfor 3 hours (tested in triplicate). The results of this ash contenttesting are displayed in Table 6, and demonstrate the increased accuracyand decreased variability of materials compounded using a twin screw,dual hopper extruder with respect to the target formulation.

TABLE 6 Average Relative Sample Bioactive Standard Standard Sample SizeGlass (%) Deviation Deviation 80/20 450G 90-150 μm 5 22.67 3.73 16.46single screw, single hopper (Compounded at Infinity) 77/23 LT3 90-150 μm5 22.71 0.33 1.46 twin screw, dual hopper (Compounded at Foster) 70/30450G 90-150 μm 6 34.95 4 11.43 single screw, single hopper (Compoundedat Infinity) 70/30 150G 90-150 μm 5 31.1 3.64 11.65 single screw, singlehopper (Compounded at Infinity) 80/20 450G 90-150 μm 3 19.49 0.12 0.60twin screw, dual hopper (Compounded at Foster) 70/30 450G 90-150 μm 329.34 0.10 0.36 twin screw, dual hopper (Compounded at Foster)

Micro-CT analysis of several bioactive composite materials of thepresent invention was performed to demonstrate the homogeneity of theglass within the polymer matrix and to quantify the surface areaexposure of bioactive glass particles. All samples were scanned on aScanco Medical pCT 40 system using an x-ray energy level of 70 Kvp andan isotropic voxel size of 6 μm. Particle analysis (volume fraction,size, distribution) was conducted using the Scanco software bundled withthe microCT system. Images were binarized to separate the particles frompolymer using a fixed threshold value. Representative images and 3-Dreconstructions of two exemplary embodiments of the present inventioncan be seen in FIGS. 86 and 87. Table 7 displays the volume % andsurface area % of glass for these two embodiments.

TABLE 7 Homogeneity Volume % Glass per (vol % in 4 Formulation Micro-CTAnalysis quadrants) 80/20 450G with 10.1% Q1: 9.83 90-150 μm CombeiteQ2: 10.01 Compounded at Q3: 10.28 Foster Q4: 10.18 70/30 450G with 18.1%Q1: 17.87 90-150 μm Combeite Q2: 18.11 Compounded at Q3: 18.20 FosterQ4: 18.35

In-Vivo Performance Testing of Bioactive Composites

Various formulations of composite implants of PEEK and Combeiteglass-ceramic made in accordance with the methods of the presentinvention were implanted in the diaphyseal region of sheep long bones(tibia and metatarsal). The bioactive composite test articles were 80/20LT1/<53 um bioactive glass (80/20S), 80/20 LT1/90-150 um bioactive glass(80/20L), 70/30 LT1/<53 um bioactive glass (70/30S), 60/40 LT3/<90 um(60/40M) bioactive glass. The negative control article was 100% PEEKOptima LT1 and the positive control article was grit-blasted titanium.The surface roughness of representative animal samples was measuredusing a non-contacting micro laser scanner and is displayed in Table 8.

TABLE 8 Surface Roughness Formulation Ra (μm) 100% PEEK 0.96Grit-blasted Titanium 1.73 80/20S 0.81 70/30S 0.62 80/20L 1.07 60/40M1.13

A push-out test was performed after 12 and 24 weeks of implantation tomeasure the interfacial shear strength between the implanted materialsand the adjacent bone as a measure of bioactivity and bone bonding.After explantation, tibiae and metatarsals were sectioned intoindividual specimens, each containing 1 defect site. All excess tissuewas removed and specimens were cut in half to expose the medial face ofthe implant. A 5 mm compression pin was used to apply an axial force ata constant displacement rate of 1 mm/min. Load and displacement wererecorded. Interfacial Shear stress was calculated by the followingequation:

$\sigma = \frac{F_{\max}}{\pi\;{Dt}}$where, Fmax is the maximum push-out force, D is the diameter of theimplant (5 mm) and t is the cortical thickness (avg. of 4 measurements).

Statistical analysis was performed using Minitab software. A Ryan-JoinerNormality test performed to confirm normal distribution of the data. Aone way ANOVA test was used to assess the interaction betweenformulation and interfacial shear strength. The Dunnett Method forTreatment vs. Control Comparisons was used to assess significancebetween the bioactive composite test groups versus the 100% PEEK controlat a 95% confidence interval.

The results of the mechanical push out testing are displayed in FIG. 88.All formulations of the bioactive composite had at least two timesgreater interfacial shear strength as compared to the 100% polymercontrol at 12 and 24 weeks. At 12 weeks, all bioactive compositeformulations except 80/20S had significantly stronger bone-bonding than100% PEEK (p<0.05). At 24 weeks the 70/30 and 60/40 bioactive compositematerials exhibited significantly greater interfacial shear strength ascompared to 100% PEEK (p<0.05). These formulations also exhibited higheraverage interfacial shear strength as compared to the grit blastedtitanium positive control, despite the higher surface roughness of thetitanium implant.

FIGS. 89 and 90 are representative histological images demonstrating thebone bonding nature of the bioactive composite upon in-vivo implantationof dowels comprised of the present invention material into sheep bone.New bone is shown adjacent to the implant without intervening fibroustissue. For instance, for the implants of FIG. 89 (histology of a 60/40LT3/<90 μm implant) and FIG. 90 (histology of a 80/20 LT1/90-150 μmimplant), new bone 2004 is observed growing into the implant 2000 atlocations along the interface 2002 where the glass is in the size rangeof about 50 microns to about 100 microns, thereby providing a mechanicalinterlock between the host bone 2010 and the bioactive composite implant2000.

Although illustrated and described above with reference to certainspecific embodiments and examples, the present invention is neverthelessnot intended to be limited to the details shown. Rather, variousmodifications may be made in the details within the scope and range ofequivalents of the claims and without departing from the spirit of theinvention. It is expressly intended, for example, that all rangesbroadly recited in this document include within their scope all narrowerranges which fall within the broader ranges.

The disclosures of each and every patent, patent application, andpublication cited herein are hereby incorporated herein by reference intheir entirety.

While this invention has been disclosed with reference to specificembodiments, it is apparent that other embodiments and variations ofthis invention may be devised by others skilled in the art withoutdeparting from the true spirit and scope of the invention. The appendedclaims are intended to be construed to include all such embodiments andequivalent variations.

The invention claimed is:
 1. A method of preparing a bioactivecomposite, comprising: a) heating polyaryletherketone polymer particlesto at least the melting temperature of the polyaryletherketone polymerto at least partially melt the polyaryletherketone polymer particles,wherein the polyaryetherketone polymer particles have a particle sizeranging from 1,000 μm to 4,000 μm prior to heating, and wherein thepolyaryletherketone polymer has a molecular weight ranging from 70,000to 120,000 Daltons prior to heating; b) adding alkali-containingbioactive glass particles to the at least partially meltedpolyaryletherketone particles, wherein the alkali-containing bioactiveglass particles have a particle size ranging from 1 μm to 500 μm; and c)extruding a bioactive composite, wherein the polyaryletherketone polymeris present in an amount of 70% to 85% by weight of the extrudedbioactive composite, and wherein the alkali-containing bioactive glassparticles is present in an amount of 15% to 30% by weight of theextruded bioactive composite.
 2. The method of claim 1, wherein prior toadding the alkali-containing bioactive glass particles, furthercomprising: mixing the at least partially melted polyaryletherketonepolymer particles.
 3. The method of claim 1, wherein thepolyaryletherketone polymer is polyetheretherketone (PEEK).
 4. Themethod of claim 3, wherein the PEEK polymer is present in an amount of70% to 80% by weight of the extruded bioactive composite, and whereinthe alkali-containing bioactive glass particles is present in an amountof 20% to 30% by weight of the extruded bioactive composite.
 5. Themethod of claim 1, wherein the alkali-containing bioactive glassparticles are 45S5 or Combeite glass-ceramic.
 6. The method of claim 1,wherein the alkali-containing bioactive glass particles have a particlesize range from 50 μm to 250 μm.
 7. The method of claim 1, wherein thecomposite is non-resorbable.
 8. The method of claim 1, wherein theamount by weight of the alkali-containing bioactive glass particles inthe extruded bioactive composite, measured in a plurality of samplestaken from the composite, has a standard deviation ranging from 0.10 to0.33.
 9. A method of preparing a homogeneous bioactive shaped body,comprising: a) heating polyaryletherketone polymer particles to at leastthe melting temperature of the polyaryletherketone polymer to at leastpartially melt the polyaryletherketone polymer particles, wherein thepolyaryetherketone polymer particles have a particle size ranging from1,000 μm to 4,000 μm prior to heating, and wherein thepolyaryletherketone polymer has a molecular weight ranging from 70,000to 120,000 Daltons prior to heating; b) adding alkali-containingbioactive glass particles to the at least partially meltedpolyaryletherketone polymer particles, wherein the alkali-containingbioactive glass particles have a particle size ranging from 1 μm to 500μm; and c) extruding homogeneous pellets of polyaryletherketone polymerand alkali-containing bioactive glass particles, wherein thepolyaryletherketone polymer is present in an amount of 70% to 80% byweight of the homogeneous pellets, and wherein the alkali-containingbioactive glass particles are present in an amount of 20% to 30% byweight of the homogeneous pellets; and d) injection molding thehomogeneous pellets to form the homogeneous bioactive shaped body. 10.The method of claim 9, wherein prior to adding the alkali-containingbioactive glass particles, further comprising: mixing the at leastpartially melted polyaryletherketone polymer particles.
 11. The methodof claim 9, wherein the polyaryletherketone polymer ispolyetheretherketone (PEEK).
 12. The method of claim 11, wherein thealkali-containing bioactive glass particles has a particle size rangefrom 50 μm to 250 μm.
 13. The method of claim 9, wherein thealkali-containing bioactive glass particles are 45S5 or Combeiteglass-ceramic.
 14. The method of claim 9, wherein the composite isnon-resorbable.
 15. A method of preparing a bioactive composite,comprising: a) heating polyetheretherketone (PEEK) polymer particles toat least the melting temperature of the PEEK polymer to at leastpartially melt the PEEK polymer particles, wherein the PEEK polymerparticles have a particle size ranging from 1,000 μm to 4,000 μm priorto heating, and wherein the PEEK polymer has a molecular weight rangingfrom 100,000 to 120,000 Daltons prior to heating; b) addingalkali-containing bioactive glass particles to the at least partiallymelted PEEK polymer particles, wherein the bioactive glass particleshave a particle size range from 1 μm to 500 μm; and c) extruding abioactive composite, wherein the PEEK polymer is present in an amount of70% to 80% by weight of the extruded bioactive composite, and whereinthe alkali-containing bioactive glass particles is present in an amountof 20% to 30% by weight of the extruded bioactive composite.
 16. Themethod of claim 15, wherein prior to adding the alkali-containingbioactive glass particles, further comprising: mixing the at leastpartially melted PEEK polymer particles.
 17. The method of claim 1,wherein the bioactive composite is dry mixed.
 18. The method of claim 9,wherein the shaped body is prepared without the use of water or asolvent.
 19. The method of claim 15, wherein the bioactive composite isdry mixed.